Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingl...Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.展开更多
Background:The correlation between the morphological structure of the patellofemoral joint(PFJ)and the severity of knee joint osteoarthritis(KOA)remains uncertain.This study aims to investigate the correlation between...Background:The correlation between the morphological structure of the patellofemoral joint(PFJ)and the severity of knee joint osteoarthritis(KOA)remains uncertain.This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs.Methods:This multi-center,retrospective study analyzed the magnetic resonance imaging(MRI)scans and anteroposterior radiographs of 534 adult outpatients with KOA.To evaluate the radiographic severity of KOA,anteroposterior radiographs of the knee and the Kellgren-Lawrence(K-L)grade were used.Knee MRI scans were used to measure the patellar length ratio(PLR),sulcus angle(SA),lateral patellar tilt angle(LPTA),and the distance between tibial tuberosity and trochlear groove(TT-TG).We examined the association between the configuration of the PFJ,arrangement,and harshness of the KOA.Information on participants’demographics,such as age,sex,side,height,and weight,was collected.A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side.Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA.Multiple linear regression models were used for the association between LPTA,SA,TT-TG,and severity of KOA after accounting for demographic variables.Results:The study comprised of 534 patients;of these,339(63%)were female.A total of 586 knees were evaluated in this study.Age showed a strong positive correlation with KOA severity(r=0.516,P<0.01),whereas LPTA showed a strong negative correlation(r=–0.662,P<0.01).Additionally,SA(r=0.616,P<0.05),and TT-TG showed a strong positive correlation(r=0.770,P<0.01)with tibiofemoral osteoarthritis(TFOA)severity.Multiple linear regression analysis indicated that knee osteoarthritis severity(β=–2.946,P<0.001)and side(β=–0.839,P=0.001)was associated with LPTA;knee osteoarthritis severity(β=5.032,P<0.001)and age(β=–0.095,P<0.001)was associated with SA;knee osteoarthritis severity(β=2.445,P<0.001),sex(β=–0.326,P=0.041),body mass index(β=–0.061,P=0.017)and age(β=–0.025,P<0.001)was associated with TT-TG.Conclusion:Radiographic severity of KOA was positively associated with age,SA,and TT-TG but negatively associated with LPTA.展开更多
The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and ...The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and the physicochemical properties of metal organic frameworks(MOFs),we prepared nanosized zinc-based MOF:Zn-BTC with the ability to slowly release Zn^(2+).In cellular levels,Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration.It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4%MRSA and 47.2%Escherichia coli.In addition,Zn-BTC also displayed the ability of lowering the expression of antioxidant genes:superoxide dismutase 1,superoxide dismutase 2 and interleukin 6,and enhancing the expression of wound healing genes:transforming growth factors-b and type I collagen.Finally,it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs.The favorable biocompatibility,antibacterial and anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.展开更多
Andrographolide(AG)has favorable anti-inflammatory and antioxidative capacity.However,it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injectio...Andrographolide(AG)has favorable anti-inflammatory and antioxidative capacity.However,it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection,leading to low therapeutic efficiency in osteoarthritis(OA).Herein,we designed a nano-sized pH-responsive drug delivery system(DDS)for OA treatment by using modified mesoporous silica nanoparticles(MSNs)with pH-responsive polyacrylic acid(PAA)for loading of AG to form AG@MSNs-PAA nanoplatform.The nanoparticles have uniform size(120 nm),high drug loading efficiency(22.3860.71%)and pH-responsive properties,beneficial to sustained release in OA environment.Compared with AG,AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1b-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model,as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss.Therefore,the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.展开更多
The presence of excessive reactive oxygen species(Ros)at a skin wound site is an important factor affecting wound healing.ROS scavenging,which regulates the ROS microenvironment,is essential for wound healing.In this ...The presence of excessive reactive oxygen species(Ros)at a skin wound site is an important factor affecting wound healing.ROS scavenging,which regulates the ROS microenvironment,is essential for wound healing.In this study,we used novel electrospun PCL/gelatin/arbutin(PCL/G/A)nanofibrous membranes as wound dressings,with PCL/gelatin(PCL/G)as the backbone,and plantderived arbutin(hydroquinone-β-D-glucopyranoside,ARB)as an effective antioxidant that scavenges ROos and inhibits bacterial infection in wounds.The loading of ARB increased the mechanical strength of the nanofibres,with a water vapour transmission rate of more than 2500g/(m^(2)×24h),and the water contact angle decreased,indicating that hydrophilicity and air permeability were significantly improved.Drug release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable degradability.Haemolysis experiments showed that the PCL/G/A nanofibre membranes were biocompatible,and DPPH and ABTS+radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant activity.In addition,haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in vivo.In vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and non-toxicity.In conclusion,we successfully prepared a multifunctional wound dressing,PCL/G/A,for skin wound healing and investigated its potential role in wound healing,which is beneficial for the clinical translational application of phytomedicines.展开更多
Cartilage defects may lead to severe degenerative joint diseases.Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair.However,the underlying mechanisms of ...Cartilage defects may lead to severe degenerative joint diseases.Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair.However,the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified.Herein,we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis.Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-b signaling pathway,and integrin-b1(ITGB1),a receptor of collagen,was highly expressed in bone marrow mesenchymal stem cells(BMSCs).Further analysis showed genes such as COL2A1 and Tenascin C(TNC)that interacted with ITGB1 were significantly enriched in extracellular matrix(ECM)structural constituents in the chondrogenic induction group.Knockdown of ITGB1 led to the downregulation of cartilage-specific genes(SOX9,ACAN,COL2A1),SMAD2 and TNC,as well as the downregulation of phosphorylation of SMAD2/3.Knockdown of TNC also resulted in the decrease of cartilage markers,ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend.Finally,in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration.In summary,we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel.It can activate TGF-SMAD2/3 signaling,followed by impacting TNC expression,which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance chondrogenesis.These may provide concernful support for cartilage tissue engineering and biomaterials development.展开更多
基金supported by National Natural Science Foundation of China(NSFC Nos.81601930 and U1613224)Natural Science Foundation of Guangxi(2016JJB140050)+1 种基金Research Grant Council of Hong Kong(HKU715213 and 17206916)Shenzhen Peacock Project
文摘Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.
基金supported by Shandong Province Medical and Health Science Technology Development Program(No.202104070134)the Guangxi Key Research and Development Plan(No.AB22035014)the Special Fund of Characteristic Innovation Team of the First Affiliated Hospital of Guangxi MedicalUniversity(No.YYZS2022003)
文摘Background:The correlation between the morphological structure of the patellofemoral joint(PFJ)and the severity of knee joint osteoarthritis(KOA)remains uncertain.This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs.Methods:This multi-center,retrospective study analyzed the magnetic resonance imaging(MRI)scans and anteroposterior radiographs of 534 adult outpatients with KOA.To evaluate the radiographic severity of KOA,anteroposterior radiographs of the knee and the Kellgren-Lawrence(K-L)grade were used.Knee MRI scans were used to measure the patellar length ratio(PLR),sulcus angle(SA),lateral patellar tilt angle(LPTA),and the distance between tibial tuberosity and trochlear groove(TT-TG).We examined the association between the configuration of the PFJ,arrangement,and harshness of the KOA.Information on participants’demographics,such as age,sex,side,height,and weight,was collected.A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side.Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA.Multiple linear regression models were used for the association between LPTA,SA,TT-TG,and severity of KOA after accounting for demographic variables.Results:The study comprised of 534 patients;of these,339(63%)were female.A total of 586 knees were evaluated in this study.Age showed a strong positive correlation with KOA severity(r=0.516,P<0.01),whereas LPTA showed a strong negative correlation(r=–0.662,P<0.01).Additionally,SA(r=0.616,P<0.05),and TT-TG showed a strong positive correlation(r=0.770,P<0.01)with tibiofemoral osteoarthritis(TFOA)severity.Multiple linear regression analysis indicated that knee osteoarthritis severity(β=–2.946,P<0.001)and side(β=–0.839,P=0.001)was associated with LPTA;knee osteoarthritis severity(β=5.032,P<0.001)and age(β=–0.095,P<0.001)was associated with SA;knee osteoarthritis severity(β=2.445,P<0.001),sex(β=–0.326,P=0.041),body mass index(β=–0.061,P=0.017)and age(β=–0.025,P<0.001)was associated with TT-TG.Conclusion:Radiographic severity of KOA was positively associated with age,SA,and TT-TG but negatively associated with LPTA.
基金supported by National Natural Science Foundation of China(Grant No.82160430)the Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD21075002,GuikeAD19254003)+2 种基金the Guangxi Scientific Research and Technological Development Foundation(Grant No.GuikeAB21220062)the Natural Science Foundation of Guangxi(Grant No.2020GXNSFAA159134)the Nanning Qingxiu District Science and Technology Major Special Project(Grant No.2020013).
文摘The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and the physicochemical properties of metal organic frameworks(MOFs),we prepared nanosized zinc-based MOF:Zn-BTC with the ability to slowly release Zn^(2+).In cellular levels,Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration.It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4%MRSA and 47.2%Escherichia coli.In addition,Zn-BTC also displayed the ability of lowering the expression of antioxidant genes:superoxide dismutase 1,superoxide dismutase 2 and interleukin 6,and enhancing the expression of wound healing genes:transforming growth factors-b and type I collagen.Finally,it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs.The favorable biocompatibility,antibacterial and anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.
基金This study was financially supported by The National key research and development program of China(2016YFB0700800)the National Natural Science Foundation of China(Grant No.81972120)the Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD19254003),the Seventh Batch of Special Experts in Guangxi(Professor Wei Yao).
文摘Andrographolide(AG)has favorable anti-inflammatory and antioxidative capacity.However,it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection,leading to low therapeutic efficiency in osteoarthritis(OA).Herein,we designed a nano-sized pH-responsive drug delivery system(DDS)for OA treatment by using modified mesoporous silica nanoparticles(MSNs)with pH-responsive polyacrylic acid(PAA)for loading of AG to form AG@MSNs-PAA nanoplatform.The nanoparticles have uniform size(120 nm),high drug loading efficiency(22.3860.71%)and pH-responsive properties,beneficial to sustained release in OA environment.Compared with AG,AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1b-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model,as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss.Therefore,the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.
基金the Guangxi Science and Technology Base andTalent Special Project(Grant No.GuikeAD19254003)Guangxi Scientific Research and Technological Development Foundation(Grant No.GuikeAB21220062)+4 种基金Guangxi University's young and middle-aged teachers'basic scientific research ability enhancement project(Grant No.2022KY0104)Open Research Fund From Guangxi Key Laboratory Of Regenerative Medicine,Guangxi Medical University(Grant No.202003)The Foundation of the Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Coconstructed by the Province and Ministry(Grant No.CICRMMBRTC-2023001)‘Medical Excellence Award'Funded By The Creative Research Development Grant From The First Affiliated Hospital of Guangxi Medical University(Grant No.202210)Guangxi Health Commission self-funded scientific research project(Grant No.Z20180949).
文摘The presence of excessive reactive oxygen species(Ros)at a skin wound site is an important factor affecting wound healing.ROS scavenging,which regulates the ROS microenvironment,is essential for wound healing.In this study,we used novel electrospun PCL/gelatin/arbutin(PCL/G/A)nanofibrous membranes as wound dressings,with PCL/gelatin(PCL/G)as the backbone,and plantderived arbutin(hydroquinone-β-D-glucopyranoside,ARB)as an effective antioxidant that scavenges ROos and inhibits bacterial infection in wounds.The loading of ARB increased the mechanical strength of the nanofibres,with a water vapour transmission rate of more than 2500g/(m^(2)×24h),and the water contact angle decreased,indicating that hydrophilicity and air permeability were significantly improved.Drug release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable degradability.Haemolysis experiments showed that the PCL/G/A nanofibre membranes were biocompatible,and DPPH and ABTS+radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant activity.In addition,haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in vivo.In vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and non-toxicity.In conclusion,we successfully prepared a multifunctional wound dressing,PCL/G/A,for skin wound healing and investigated its potential role in wound healing,which is beneficial for the clinical translational application of phytomedicines.
基金supported by the Guangxi Scientific Research and Technological Development Foundation(grant number GuikeAB23026049)Guangxi Natural Science Foundation(grant number 2023GXNSFBA026034)the National Natural Science Foundation of China(grant number 82360426).
文摘Cartilage defects may lead to severe degenerative joint diseases.Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair.However,the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified.Herein,we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis.Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-b signaling pathway,and integrin-b1(ITGB1),a receptor of collagen,was highly expressed in bone marrow mesenchymal stem cells(BMSCs).Further analysis showed genes such as COL2A1 and Tenascin C(TNC)that interacted with ITGB1 were significantly enriched in extracellular matrix(ECM)structural constituents in the chondrogenic induction group.Knockdown of ITGB1 led to the downregulation of cartilage-specific genes(SOX9,ACAN,COL2A1),SMAD2 and TNC,as well as the downregulation of phosphorylation of SMAD2/3.Knockdown of TNC also resulted in the decrease of cartilage markers,ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend.Finally,in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration.In summary,we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel.It can activate TGF-SMAD2/3 signaling,followed by impacting TNC expression,which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance chondrogenesis.These may provide concernful support for cartilage tissue engineering and biomaterials development.
