NF-κBp50/p52 double knockout （dKO） and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have os...NF-κBp50/p52 double knockout （dKO） and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from pS0/ p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.展开更多
Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of ...Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor （IR） selectively in chondrocytes （CartIR-/-） had no discernable differences in total femoral length compared to control littermates. However, CartIR-/- mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor （IGF）-IR mRNA and protein levels. Subsequently, IGF-1 induced phosphorylafion of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR-/- mice when compared with that of the control littermates, which was associated with upregnlation of tuberous sclerosis complex 2 （TSC2）. These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.展开更多
Background： Fibroblast growth factor receptor 3 （FGFR3） inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and s...Background： Fibroblast growth factor receptor 3 （FGFR3） inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone （1-3） plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase （TERT） and RNA component of telomerase （TR）, and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response. Results： Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity （p 〈 0.0.5）. Chondrocytes treated with T3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity （p 〈 0.05）; TERT and TR were not significantly reduced. The action of T3 at the growth plate may be partially mediated through the FGFR3 pathway. Conclusions： The results suggest that FGFR3 inhibits chondrocyte proliferation and reducing telomerase activity indicating an important role for telomerase in capacity during bone elongation. by down-regulating TERT expression sustaining chondrocyte proliferative展开更多
Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis ...Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image’s plane of focus, and lack of cell-specific features, interfered with identification of cells. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes’ number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CKO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth.展开更多
The growth plate is a thin layer of cartilage sandwiched between epiphyseal and metaphyseal bone and is the location of active bone growth during childhood. It is subjected to large compressive and shear forces while ...The growth plate is a thin layer of cartilage sandwiched between epiphyseal and metaphyseal bone and is the location of active bone growth during childhood. It is subjected to large compressive and shear forces while protecting its resident chondrocytes from damage. We believe that computational modeling can help us better understand how the macro-scale loads are transmitted to micro-scale stresses and strains within the growth plate cartilage. As a first step in this process we analyzed the mechanical response of compression experiments performed on bovine bone/growth plate/bone samples. We endeavored to estimate the modulus of elasticity of the growth plate itself by simulating the compression experiments of these specimens using the finite element method. It is shown that when the growth plate in the compression specimens was modeled as a flat layer, the state of stress in the cartilage was triaxial and non-uniform with the hydrostatic stress being much greater than the octahedral shear stress over most of the central region of the growth plate test samples. The computational models accounted for variations in the average cartilage thickness, the non-uniaxial, non-uniform and triaxial state of stress in the thin cartilage layer, and for the estimated extrinsic compliance resulting from compression of the variable heights of bone on either side of the growth plate cartilage. However, due to lack of information on the internal structure of each sample, the models did not account for the variations in the non-flat topography of the growth plates. The models also did not include the calcified cartilage layer. Further model development is recommendedin order to determine the degree to which accounting for the complex growth plate topography influences the predicted cartilage modulus of elasticity.展开更多
Infantile Blount's disease is a condition that causes genu varum and internal tibial torsion. Treatment options include observation, orthotics, corrective osteotomy, elevation of the medial tibial plateau, resecti...Infantile Blount's disease is a condition that causes genu varum and internal tibial torsion. Treatment options include observation, orthotics, corrective osteotomy, elevation of the medial tibial plateau, resection of a physeal bar, lateral hemi-epiphysiodesis, and guided growth of the proximal tibial physis. Each of these treatment options has its disadvantages. Treating the coronal deformity alone(genu varum) will result in persistence of the internal tibial torsion(the axial deformity). In this report, we describe the combination of lateral growth modulation and distal tibial external rotation osteotomy to correct all the elements of the disease. This has not been described before for treatment of Blount's disease. Both coronal and axial deformities were corrected in this patient. We propose this combination(rather than the lateral growth modulation alone) as the method of treatment for early stages of Blount's disease as it corrects both elements of the disease and in the same time avoids the complications of proximal tibial osteotomy.展开更多
The growth plate is crucial for skeletal growth in children,but research on repairing growth plate damage and restoring growth is limited.Here,a high-toughness adaptive dualcrosslinked hydrogel is designed to mimic th...The growth plate is crucial for skeletal growth in children,but research on repairing growth plate damage and restoring growth is limited.Here,a high-toughness adaptive dualcrosslinked hydrogel is designed to mimic the growth plate's structure,supporting regeneration and bone growth.Composed of aldehyde-modified bacterial cellulose(DBNC),methacrylated gelatin(GelMA)and sodium alginate(Alg),the hydrogel is engineered through ionic bonding and Schiff base reactions,creating a macroporous structure.This structure can transform into a denser form by binding with calcium ions.In vitro,the loose macroporous structure of the hydrogels can promote chondrogenic differentiation,and when it forms a dense structure by binding with calcium ions,it also can activate relevant chondrogenic signaling pathways under the influence of insulin-like growth factor I(IGF-1),further inhibiting osteogenesis.In vivo experiments in a rat model of growth plate injury demonstrated that the hydrogel promoted growth plate cartilage regeneration and minimized bone bridge formation by creating a hypoxic microenvironment that activates IGF-1-related pathways.This environment encourages chondrogenic differentiation while preventing the undesired formation of bone tissue within the growth plate area.Overall,the dual-crosslinked hydrogel not only mimics the growth plate's structure but also facilitates localized IGF-1 expression,effectively reshaping the growth plate's function.This approach represents a promising therapeutic strategy for treating growth plate injuries,potentially addressing challenges associated with skeletal growth restoration in pediatric patients.展开更多
The origin of bone marrow osteoblasts is not totally understood.Recent findings demonstrated that bone marrow osteoblasts could be derived from a subpopulation of hypertrophic Col2^(+)/Col10^(+)chondrocytes which migr...The origin of bone marrow osteoblasts is not totally understood.Recent findings demonstrated that bone marrow osteoblasts could be derived from a subpopulation of hypertrophic Col2^(+)/Col10^(+)chondrocytes which migrate from the growth plate into the bone marrow cavity underneath the growth plate and dedifferentiate into mesenchymal progenitor cells and then differentiate into mature osteoblasts.1 This process is called chondrocyte-osteoblast transdifferentiation.This type of osteoblast participates in bone formation and is involved in maintaining bone remodeling,especially in the epiphyseal and diaphyseal regions of long bone.Several growth factors,such as Ihh,PTH,and Wnt signaling molecules have been demonstrated to play a critical role in the regulation of chondrocyte-osteoblast transdifferentiation2;however,the role of Runx2,the key transcription factor controlling skeletal development,3 in chondrocyte-osteoblast transdifferentiation has not been fully defined.展开更多
The growth plate plays a crucial role in long bone development and elongation,housing stem cells that contribute to bone formation.This study investigates the role of primary cilia,specialized organelles that regulate...The growth plate plays a crucial role in long bone development and elongation,housing stem cells that contribute to bone formation.This study investigates the role of primary cilia,specialized organelles that regulate stem cell fate,in the development and repair of long bones.Here,we report the presence of primary cilia in all zones of the growth plate,particularly during embryonic development.Spatial transcriptomics and analysis of conditional knockout(CKO)mice identified that primary cilia mediate critical developmental signaling pathways within the growth plate.Disruption of primary cilia in growth plate chondroblasts or osteoblasts impaired long bone development by activating the Wnt signaling pathway and disrupting the cellular stemness.This resulted in elevated Mmp13 secretion,abnormal mineralization,and structural defects,ultimately hindering bone elongation.Time-lapse imaging showed an increased frequency of abnormal mitosis and a reduced rate of asymmetric division in skeletal stem cells(SSCs)from CKO mice.In conclusion,our findings indicated that primary cilia are critical for long bone development,regulating stem cell fate through key signaling pathways.Loss of primary cilia leads to excessive Wnt signaling and disruption of SSC stemness,impairing bone elongation.This study highlights the essential role of primary cilia in bone development and suggests potential therapeutic targets for skeletal disorders.展开更多
Growth plate cartilage has limited self-repair ability,leading to poor bone bridge formation post-injury and ultimately limb growth defects in children.The current corrective surgeries are highly invasive,and outcomes...Growth plate cartilage has limited self-repair ability,leading to poor bone bridge formation post-injury and ultimately limb growth defects in children.The current corrective surgeries are highly invasive,and outcomes can be unpredictable.Following growth plate injury,the direct loss of extracellular matrix(ECM)coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration.We designed an exosome(Exo)derived from bone marrow mesenchymal stem cells(BMSCs)loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties.Aldehyde-functionalized chondroitin sulfate(OCS)was introduced into gelatin methacryloyl(GM)to form GMOCS hydrogel.Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS.In addition,the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling.展开更多
The application of the adaptive growth method is limited because several key techniques during the design process need manual intervention of designers. Key techniques of the method including the ground structure cons...The application of the adaptive growth method is limited because several key techniques during the design process need manual intervention of designers. Key techniques of the method including the ground structure construction and seed selection are studied, so as to make it possible to improve the effectiveness and applicability of the adaptive growth method in stiffener layout design optimization of plates and shells. Three schemes of ground structures, which are comprised by different shell elements and beam elements, are proposed. It is found that the main stiffener layouts resulted from different ground structures are almost the same, but the ground structure comprised by 8-nodes shell elements and both 3-nodes and 2-nodes beam elements can result in clearest stiffener layout, and has good adaptability and low computational cost. An automatic seed selection approach is proposed, which is based on such selection rules that the seeds should be positioned on where the structural strain energy is great for the minimum compliance problem, and satisfy the dispersancy requirement. The adaptive growth method with the suggested key techniques is integrated into an ANSYS-based program, which provides a design tool for the stiffener layout design optimization of plates and shells. Typical design examples, including plate and shell structures to achieve minimum compliance and maximum bulking stability are illustrated. In addition, as a practical mechanical structural design example, the stiffener layout of an inlet structure for a large-scale electrostatic precipitator is also demonstrated. The design results show that the adaptive growth method integrated with the suggested key techniques can effectively and flexibly deal with stiffener layout design problem for plates and shells with complex geometrical shape and loading conditions to achieve various design objectives, thus it provides a new solution method for engineering structural topology design optimization.展开更多
In the presenl paper. the finite deformation and stress analysis for a hyperelasticrectangular plate with a center void under a uniaxial extension is studied. In order toconsider the effect of the exijtence of the voi...In the presenl paper. the finite deformation and stress analysis for a hyperelasticrectangular plate with a center void under a uniaxial extension is studied. In order toconsider the effect of the exijtence of the void on the deformation and stress of theplate, the problem is reduced to the deformation and stress analysis for a hyperelusticannular plate and its approximate solution is obtained from the minimum potentialenergy principle. The growth of the cavitation iS also nunterically computed andanalysed.展开更多
A study of postbuckling and delamination propagation behavior in delaminated stiffened composite plates was presented. A methodology was proposed for simulating the multi-failure responses, such as initial and postbuc...A study of postbuckling and delamination propagation behavior in delaminated stiffened composite plates was presented. A methodology was proposed for simulating the multi-failure responses, such as initial and postbuckling, delamination onset and propagation, etc. A finite element analysis was conducted on the basis of the Mindlin first order shear effect theory and the von-Krmn nonlinear deformation assumption. The total energy release rate used as the criteria of delamination growth was estimated with virtual crack closure technique (VCCT). A self-adaptive grid moving technology was adopted to model the delamination growth process. Moreover, the contact effect along delamination front was also considered during the numerical simulation process. By some numerical examples, the influence of distribution and location of stiffener, configuration and size of the delamination, boundary condition and contact effect upon the delamination growth behavior of the stiffened composite plates were investigated. The method and numerical conclusion provided should be of great value to engineers dealing with composite structures.展开更多
BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate ...BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.展开更多
The analyses of finite deformation and stress for a hyperelastic rectangular plate with some voids under an uniaxial extension were conducted. The governing differential equations were given from the incompressibility...The analyses of finite deformation and stress for a hyperelastic rectangular plate with some voids under an uniaxial extension were conducted. The governing differential equations were given from the incompressibility condition of the material. The solution was approximately obtained from the minimum potential energy principle. The growth of voids was discussed. One can see that an initial central circular-cylinder void becomes an elliptic-cylinder void, but an initial non-centeral circular-cylinder void becomes an elliptic-like cylinder void and the center of void has a shift. The stress distributions along the edges of voids were given and the phenomenon of stress concentration was observed. The influences of the distribution manner and size of voids, as well as the distance between them on the growth of voids were analyzed.展开更多
The 6061-T651 aluminium alloy is one of the most common aluminium alloys for marine components and general structures. The stress intensity factor (SIF) is an important parameter for estimating the life of the cracked...The 6061-T651 aluminium alloy is one of the most common aluminium alloys for marine components and general structures. The stress intensity factor (SIF) is an important parameter for estimating the life of the cracked structure. In this paper, the stress intensity factors of a slant-cracked plate, which is made of 6061-T651 aluminum, have been calculated using extended finite element method (XFEM) and finite element method (FEM) in ABAQUS software and the results were compared with theoretical values. Numerical values obtained from these two methods were close to the theoretical values. In simulations of crack growth at different crack angles, the crack propagation angle values were closer to the theoretical values in XFEM method. Also, the accuracy and validity of fatigue crack growth curve were much closer to the theoretical graph in XFEM than the FEM. Therefore, in this paper the capabilities of XFEM were realized in analyzing issues such as cracks.展开更多
OBJECTIVE:This study was conducted to evaluate the effect of Amomum villosum on longitudinal bone growth.METHODS:Adolescent female Sprague-Dawley rats were divided into 3 groups and treated for 4 days:control(distille...OBJECTIVE:This study was conducted to evaluate the effect of Amomum villosum on longitudinal bone growth.METHODS:Adolescent female Sprague-Dawley rats were divided into 3 groups and treated for 4 days:control(distilled water,p.o.),recombinant human growth hormone(rhGH;100 μg/kg,s.c.),and A.villosum(500 mg/kg,p.o.) groups.On day 3,tetracycline(20 g/kg,i.p.) was injected for growth plate identification.On days 2,3 and 4,5-bromo-2'-deoxyuridine(BrdU)(50 mg/kg,i.p.) was injected to label proliferating cells.On day 5,tibias were dissected and fixed in 4% paraformaldehyde,dehydrated,and sectioned for immunohistochemistry and histomorphometry.RESULTS:The rate of bone growth in the A.villosum and rhGH groups increased to(410 ± 44) and(389 ± 46) μm/day(P<0.01),respectively,as compared with the control(330.7 ± 34.7) μm/day.The thickness of the growth plates also increased to(591 ± 37) and(598 ± 32) μm,respectively,as compared with the control(524± 89) μm(P<0.001).The number of BrdU-positive cells in the chondrocytes of the A.villosum and rhGH groups was also significantly higher(126±24) and(143±18) cells/mm 2,respectively) than in the control(109 ± 25) mm 2(P<0.05).Insulin-like growth factor-1 and bone morphogenetic protein-2 in the A.villosum and rhGH groups were highly expressed in the growth plate as compared with the control samples,indicating increased bone formation.CONCLUSIONS:A.villosum could be used to treat growth retardation during adolescence.展开更多
The growth behavior at the early stage of bainitic transformation was investigated using optical microscopy,X-ray diffraction analysis and transmission electronic microscopy.The bainite was obtained by isothermal tran...The growth behavior at the early stage of bainitic transformation was investigated using optical microscopy,X-ray diffraction analysis and transmission electronic microscopy.The bainite was obtained by isothermal transformation at 200 ℃ only for a short time in a high carbon silicon-containing steel after austenitization at 200 ℃ only for 20 min.Transmission electronic microscopy shows that the bainite appears in the form of plates with a width of about 30 nm,and that the interface of the bainite leading tip is wedge shaped.X-ray diffraction analysis reveals that the bainite plates consist of single ferrite phase,with absence of carbides.The results confirm the occurrence of the moiré which suggests the existence of austenite grain boundaries at the bainite leading tip.Both the lateral growth and longitudinal growth of bainite have weak ability to traverse the lattice-distortion strain fields and austenite grain boundary.The austenite grain boundary impedes the longitudinal growth of the bainite plate,i.e.,the growth of bainite plate stops at the austenite grain boundary.The longitudinal growth of bainite associated with the features of shear mechanism can not completely be in accordance with that of martensitic transformation.展开更多
Background: Chondrocytes in the growth plate(GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significan...Background: Chondrocytes in the growth plate(GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significant variable in understanding the mechanism of long bone growth.Methods: Forty-five postnatal Sprague-Dawley rat pups, 7-15 days old were divided into nine age groups(P7-P15). Five pups were allocated to each group. The rats were sacrificed and tibia and metatarsal bones were harvested. Bone lengths were measured after 0, 24, 48, and 72 hours of ex vivo incubation. Histology of bones was carried out, and GP lengths and chondrocyte densities were determined.Results: There were significant differences in bone length among the age groups after 0 and 72 hours of incubation. Histological sectioning was possible in metatarsal bone from all age groups, and in tibia from 7-to 13-day-old rats. No significant differences in tibia and metatarsal GP lengths were seen among different age groups at 0 and 72 hours of incubation. Significant differences in chondrocyte densities along the epiphyseal GP of the bones between 0 and 72 hours of incubation were observed in most of the age groups.Conclusion: Ex vivo growth of tibia and metatarsal bones of rats aged 7-15 days old is possible, with percentage growth rates of 23.87 ± 0.80% and 40.38 ± 0.95%measured in tibia and metatarsal bone, respectively. Histological sectioning of bones was carried out without the need for decalcification in P7-P13 tibia and P7-P15 metatarsal bone. Increases in chondrocyte density along the GP influence overall bone elongation.展开更多
基金supported by research grants from the National Institutes of Health PHS awards(AR48697 and AR63650 to LX,AR055915 to DC,and AR43510 and AR49305 to BFB)
文摘NF-κBp50/p52 double knockout （dKO） and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from pS0/ p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.
基金supported by the Hong Kong Research Grant Council General Research Fund (RGC GRF 475311)National Natural Science Foundation of China (NSFC81171717, 81130034)+1 种基金Shenzhen Strategic Development Fund (GJHS20120702105445379)the Chinese University of Hong Kong Direct Grant 2041545 to CW
文摘Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor （IR） selectively in chondrocytes （CartIR-/-） had no discernable differences in total femoral length compared to control littermates. However, CartIR-/- mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor （IGF）-IR mRNA and protein levels. Subsequently, IGF-1 induced phosphorylafion of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR-/- mice when compared with that of the control littermates, which was associated with upregnlation of tuberous sclerosis complex 2 （TSC2）. These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.
基金supported by W.K. Kellogg Endowmentthe infrastructure support of the Department of Animal Science, College of Agricultural and Environmental Sciences+1 种基金the California Agricultural Experiment Station of the University of California-Davis(CA-D*-ASC-5256-AH)financial assistance from Scholarships funded by the Ford Family Foundation and the endowment of G. Kirk Swingle
文摘Background： Fibroblast growth factor receptor 3 （FGFR3） inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone （1-3） plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase （TERT） and RNA component of telomerase （TR）, and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response. Results： Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity （p 〈 0.0.5）. Chondrocytes treated with T3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity （p 〈 0.05）; TERT and TR were not significantly reduced. The action of T3 at the growth plate may be partially mediated through the FGFR3 pathway. Conclusions： The results suggest that FGFR3 inhibits chondrocyte proliferation and reducing telomerase activity indicating an important role for telomerase in capacity during bone elongation. by down-regulating TERT expression sustaining chondrocyte proliferative
文摘Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image’s plane of focus, and lack of cell-specific features, interfered with identification of cells. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes’ number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CKO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth.
文摘The growth plate is a thin layer of cartilage sandwiched between epiphyseal and metaphyseal bone and is the location of active bone growth during childhood. It is subjected to large compressive and shear forces while protecting its resident chondrocytes from damage. We believe that computational modeling can help us better understand how the macro-scale loads are transmitted to micro-scale stresses and strains within the growth plate cartilage. As a first step in this process we analyzed the mechanical response of compression experiments performed on bovine bone/growth plate/bone samples. We endeavored to estimate the modulus of elasticity of the growth plate itself by simulating the compression experiments of these specimens using the finite element method. It is shown that when the growth plate in the compression specimens was modeled as a flat layer, the state of stress in the cartilage was triaxial and non-uniform with the hydrostatic stress being much greater than the octahedral shear stress over most of the central region of the growth plate test samples. The computational models accounted for variations in the average cartilage thickness, the non-uniaxial, non-uniform and triaxial state of stress in the thin cartilage layer, and for the estimated extrinsic compliance resulting from compression of the variable heights of bone on either side of the growth plate cartilage. However, due to lack of information on the internal structure of each sample, the models did not account for the variations in the non-flat topography of the growth plates. The models also did not include the calcified cartilage layer. Further model development is recommendedin order to determine the degree to which accounting for the complex growth plate topography influences the predicted cartilage modulus of elasticity.
文摘Infantile Blount's disease is a condition that causes genu varum and internal tibial torsion. Treatment options include observation, orthotics, corrective osteotomy, elevation of the medial tibial plateau, resection of a physeal bar, lateral hemi-epiphysiodesis, and guided growth of the proximal tibial physis. Each of these treatment options has its disadvantages. Treating the coronal deformity alone(genu varum) will result in persistence of the internal tibial torsion(the axial deformity). In this report, we describe the combination of lateral growth modulation and distal tibial external rotation osteotomy to correct all the elements of the disease. This has not been described before for treatment of Blount's disease. Both coronal and axial deformities were corrected in this patient. We propose this combination(rather than the lateral growth modulation alone) as the method of treatment for early stages of Blount's disease as it corrects both elements of the disease and in the same time avoids the complications of proximal tibial osteotomy.
基金sponsored by the National Natural Science Foundation of China(U23A20406/32301095)Shanghai Science and Technology Program(22YF1441700)Shanghai Municipal Health Commission(20244Y0178).
文摘The growth plate is crucial for skeletal growth in children,but research on repairing growth plate damage and restoring growth is limited.Here,a high-toughness adaptive dualcrosslinked hydrogel is designed to mimic the growth plate's structure,supporting regeneration and bone growth.Composed of aldehyde-modified bacterial cellulose(DBNC),methacrylated gelatin(GelMA)and sodium alginate(Alg),the hydrogel is engineered through ionic bonding and Schiff base reactions,creating a macroporous structure.This structure can transform into a denser form by binding with calcium ions.In vitro,the loose macroporous structure of the hydrogels can promote chondrogenic differentiation,and when it forms a dense structure by binding with calcium ions,it also can activate relevant chondrogenic signaling pathways under the influence of insulin-like growth factor I(IGF-1),further inhibiting osteogenesis.In vivo experiments in a rat model of growth plate injury demonstrated that the hydrogel promoted growth plate cartilage regeneration and minimized bone bridge formation by creating a hypoxic microenvironment that activates IGF-1-related pathways.This environment encourages chondrogenic differentiation while preventing the undesired formation of bone tissue within the growth plate area.Overall,the dual-crosslinked hydrogel not only mimics the growth plate's structure but also facilitates localized IGF-1 expression,effectively reshaping the growth plate's function.This approach represents a promising therapeutic strategy for treating growth plate injuries,potentially addressing challenges associated with skeletal growth restoration in pediatric patients.
基金supported by the National Key Research and Development Program of China(No.2022YFA1207500)the National Natural Science Foundation of China(No.82394445 to D.C.and L.T.,82250710174 and 82030067 to D.C.,82161160342 to D.C.and L.Q.)the Shenzhen Science and Technology Research Funding(No.JCYJ20220818101414032 to L.T.,JSGGKQTD20210831174330015 to D.C.).
文摘The origin of bone marrow osteoblasts is not totally understood.Recent findings demonstrated that bone marrow osteoblasts could be derived from a subpopulation of hypertrophic Col2^(+)/Col10^(+)chondrocytes which migrate from the growth plate into the bone marrow cavity underneath the growth plate and dedifferentiate into mesenchymal progenitor cells and then differentiate into mature osteoblasts.1 This process is called chondrocyte-osteoblast transdifferentiation.This type of osteoblast participates in bone formation and is involved in maintaining bone remodeling,especially in the epiphyseal and diaphyseal regions of long bone.Several growth factors,such as Ihh,PTH,and Wnt signaling molecules have been demonstrated to play a critical role in the regulation of chondrocyte-osteoblast transdifferentiation2;however,the role of Runx2,the key transcription factor controlling skeletal development,3 in chondrocyte-osteoblast transdifferentiation has not been fully defined.
基金supported by National Key R&D Program of China(2022YFA1103200)National,Natural Science Foundation Projects of China(U23A20444,82270963,82425014,82301048)+2 种基金Shanghai Municipal Education Commission Scientific Research Innovation Plan Project(2023ZKZD29)China Postdoctoral Science Foundation General Project(2022M722406)Shanghai Science and Technology Innovation Action Plan:Qimingxing Project(Sailing Special Program,23YF1450500).
文摘The growth plate plays a crucial role in long bone development and elongation,housing stem cells that contribute to bone formation.This study investigates the role of primary cilia,specialized organelles that regulate stem cell fate,in the development and repair of long bones.Here,we report the presence of primary cilia in all zones of the growth plate,particularly during embryonic development.Spatial transcriptomics and analysis of conditional knockout(CKO)mice identified that primary cilia mediate critical developmental signaling pathways within the growth plate.Disruption of primary cilia in growth plate chondroblasts or osteoblasts impaired long bone development by activating the Wnt signaling pathway and disrupting the cellular stemness.This resulted in elevated Mmp13 secretion,abnormal mineralization,and structural defects,ultimately hindering bone elongation.Time-lapse imaging showed an increased frequency of abnormal mitosis and a reduced rate of asymmetric division in skeletal stem cells(SSCs)from CKO mice.In conclusion,our findings indicated that primary cilia are critical for long bone development,regulating stem cell fate through key signaling pathways.Loss of primary cilia leads to excessive Wnt signaling and disruption of SSC stemness,impairing bone elongation.This study highlights the essential role of primary cilia in bone development and suggests potential therapeutic targets for skeletal disorders.
基金supported by the Natural Science Foundation of Guangdong Province(No.2020A1515011369).
文摘Growth plate cartilage has limited self-repair ability,leading to poor bone bridge formation post-injury and ultimately limb growth defects in children.The current corrective surgeries are highly invasive,and outcomes can be unpredictable.Following growth plate injury,the direct loss of extracellular matrix(ECM)coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration.We designed an exosome(Exo)derived from bone marrow mesenchymal stem cells(BMSCs)loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties.Aldehyde-functionalized chondroitin sulfate(OCS)was introduced into gelatin methacryloyl(GM)to form GMOCS hydrogel.Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS.In addition,the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling.
基金supported by National Natural Science Foundation of China(Grants No.50875174,51175347)Innovation Program of Shanghai Municipal Education Commission(Grant No.13ZZ114)Capacity Building Project of Local University of Shanghai Municipal Science and Technology Commission(Grant No.13160502500)
文摘The application of the adaptive growth method is limited because several key techniques during the design process need manual intervention of designers. Key techniques of the method including the ground structure construction and seed selection are studied, so as to make it possible to improve the effectiveness and applicability of the adaptive growth method in stiffener layout design optimization of plates and shells. Three schemes of ground structures, which are comprised by different shell elements and beam elements, are proposed. It is found that the main stiffener layouts resulted from different ground structures are almost the same, but the ground structure comprised by 8-nodes shell elements and both 3-nodes and 2-nodes beam elements can result in clearest stiffener layout, and has good adaptability and low computational cost. An automatic seed selection approach is proposed, which is based on such selection rules that the seeds should be positioned on where the structural strain energy is great for the minimum compliance problem, and satisfy the dispersancy requirement. The adaptive growth method with the suggested key techniques is integrated into an ANSYS-based program, which provides a design tool for the stiffener layout design optimization of plates and shells. Typical design examples, including plate and shell structures to achieve minimum compliance and maximum bulking stability are illustrated. In addition, as a practical mechanical structural design example, the stiffener layout of an inlet structure for a large-scale electrostatic precipitator is also demonstrated. The design results show that the adaptive growth method integrated with the suggested key techniques can effectively and flexibly deal with stiffener layout design problem for plates and shells with complex geometrical shape and loading conditions to achieve various design objectives, thus it provides a new solution method for engineering structural topology design optimization.
文摘In the presenl paper. the finite deformation and stress analysis for a hyperelasticrectangular plate with a center void under a uniaxial extension is studied. In order toconsider the effect of the exijtence of the void on the deformation and stress of theplate, the problem is reduced to the deformation and stress analysis for a hyperelusticannular plate and its approximate solution is obtained from the minimum potentialenergy principle. The growth of the cavitation iS also nunterically computed andanalysed.
文摘A study of postbuckling and delamination propagation behavior in delaminated stiffened composite plates was presented. A methodology was proposed for simulating the multi-failure responses, such as initial and postbuckling, delamination onset and propagation, etc. A finite element analysis was conducted on the basis of the Mindlin first order shear effect theory and the von-Krmn nonlinear deformation assumption. The total energy release rate used as the criteria of delamination growth was estimated with virtual crack closure technique (VCCT). A self-adaptive grid moving technology was adopted to model the delamination growth process. Moreover, the contact effect along delamination front was also considered during the numerical simulation process. By some numerical examples, the influence of distribution and location of stiffener, configuration and size of the delamination, boundary condition and contact effect upon the delamination growth behavior of the stiffened composite plates were investigated. The method and numerical conclusion provided should be of great value to engineers dealing with composite structures.
文摘BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.
文摘The analyses of finite deformation and stress for a hyperelastic rectangular plate with some voids under an uniaxial extension were conducted. The governing differential equations were given from the incompressibility condition of the material. The solution was approximately obtained from the minimum potential energy principle. The growth of voids was discussed. One can see that an initial central circular-cylinder void becomes an elliptic-cylinder void, but an initial non-centeral circular-cylinder void becomes an elliptic-like cylinder void and the center of void has a shift. The stress distributions along the edges of voids were given and the phenomenon of stress concentration was observed. The influences of the distribution manner and size of voids, as well as the distance between them on the growth of voids were analyzed.
文摘The 6061-T651 aluminium alloy is one of the most common aluminium alloys for marine components and general structures. The stress intensity factor (SIF) is an important parameter for estimating the life of the cracked structure. In this paper, the stress intensity factors of a slant-cracked plate, which is made of 6061-T651 aluminum, have been calculated using extended finite element method (XFEM) and finite element method (FEM) in ABAQUS software and the results were compared with theoretical values. Numerical values obtained from these two methods were close to the theoretical values. In simulations of crack growth at different crack angles, the crack propagation angle values were closer to the theoretical values in XFEM method. Also, the accuracy and validity of fatigue crack growth curve were much closer to the theoretical graph in XFEM than the FEM. Therefore, in this paper the capabilities of XFEM were realized in analyzing issues such as cracks.
基金Supported by the Fund of Amomum villosum in bone growth
文摘OBJECTIVE:This study was conducted to evaluate the effect of Amomum villosum on longitudinal bone growth.METHODS:Adolescent female Sprague-Dawley rats were divided into 3 groups and treated for 4 days:control(distilled water,p.o.),recombinant human growth hormone(rhGH;100 μg/kg,s.c.),and A.villosum(500 mg/kg,p.o.) groups.On day 3,tetracycline(20 g/kg,i.p.) was injected for growth plate identification.On days 2,3 and 4,5-bromo-2'-deoxyuridine(BrdU)(50 mg/kg,i.p.) was injected to label proliferating cells.On day 5,tibias were dissected and fixed in 4% paraformaldehyde,dehydrated,and sectioned for immunohistochemistry and histomorphometry.RESULTS:The rate of bone growth in the A.villosum and rhGH groups increased to(410 ± 44) and(389 ± 46) μm/day(P<0.01),respectively,as compared with the control(330.7 ± 34.7) μm/day.The thickness of the growth plates also increased to(591 ± 37) and(598 ± 32) μm,respectively,as compared with the control(524± 89) μm(P<0.001).The number of BrdU-positive cells in the chondrocytes of the A.villosum and rhGH groups was also significantly higher(126±24) and(143±18) cells/mm 2,respectively) than in the control(109 ± 25) mm 2(P<0.05).Insulin-like growth factor-1 and bone morphogenetic protein-2 in the A.villosum and rhGH groups were highly expressed in the growth plate as compared with the control samples,indicating increased bone formation.CONCLUSIONS:A.villosum could be used to treat growth retardation during adolescence.
基金Item Sponsored by Tianjin Momentous Technology Supporting Program Foundation of China(11ZCKFGX20500)
文摘The growth behavior at the early stage of bainitic transformation was investigated using optical microscopy,X-ray diffraction analysis and transmission electronic microscopy.The bainite was obtained by isothermal transformation at 200 ℃ only for a short time in a high carbon silicon-containing steel after austenitization at 200 ℃ only for 20 min.Transmission electronic microscopy shows that the bainite appears in the form of plates with a width of about 30 nm,and that the interface of the bainite leading tip is wedge shaped.X-ray diffraction analysis reveals that the bainite plates consist of single ferrite phase,with absence of carbides.The results confirm the occurrence of the moiré which suggests the existence of austenite grain boundaries at the bainite leading tip.Both the lateral growth and longitudinal growth of bainite have weak ability to traverse the lattice-distortion strain fields and austenite grain boundary.The austenite grain boundary impedes the longitudinal growth of the bainite plate,i.e.,the growth of bainite plate stops at the austenite grain boundary.The longitudinal growth of bainite associated with the features of shear mechanism can not completely be in accordance with that of martensitic transformation.
基金Ministry of Higher Education Malaysia,Grant/Award Number:FRGS/1/2012/SGO5/UPM/02/9
文摘Background: Chondrocytes in the growth plate(GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significant variable in understanding the mechanism of long bone growth.Methods: Forty-five postnatal Sprague-Dawley rat pups, 7-15 days old were divided into nine age groups(P7-P15). Five pups were allocated to each group. The rats were sacrificed and tibia and metatarsal bones were harvested. Bone lengths were measured after 0, 24, 48, and 72 hours of ex vivo incubation. Histology of bones was carried out, and GP lengths and chondrocyte densities were determined.Results: There were significant differences in bone length among the age groups after 0 and 72 hours of incubation. Histological sectioning was possible in metatarsal bone from all age groups, and in tibia from 7-to 13-day-old rats. No significant differences in tibia and metatarsal GP lengths were seen among different age groups at 0 and 72 hours of incubation. Significant differences in chondrocyte densities along the epiphyseal GP of the bones between 0 and 72 hours of incubation were observed in most of the age groups.Conclusion: Ex vivo growth of tibia and metatarsal bones of rats aged 7-15 days old is possible, with percentage growth rates of 23.87 ± 0.80% and 40.38 ± 0.95%measured in tibia and metatarsal bone, respectively. Histological sectioning of bones was carried out without the need for decalcification in P7-P13 tibia and P7-P15 metatarsal bone. Increases in chondrocyte density along the GP influence overall bone elongation.
