Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the cranio...Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues.The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells.Initially,we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells.Moreover,Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line.In addition,micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo.Unexpectedly,Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2,Dlx5,Msx2,and Osterix,but led to upregulation of Alp and Osteocalcin (OCN),both of which play critical roles in promoting osteoblast maturation.Importantly,luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity.Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis,we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes.Based on these findings,we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene,suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.展开更多
The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specificall...The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.展开更多
AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study ...AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study was conducted on 140 subjects classified into two groups, 70 with T2D and 70 HS. Medical history and physical examination with anthropometric measurements were obtained from all subjects. Body fat percentage was determined by bioelectrical impendency analysis. Serum uc OC concentration was determined by enzyme immunoassay,while serum levels of insulin and hsC RP were obtained using high sensitivity enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment-IR. Lipid profile [triglycerides,total cholesterol(TC), high-density lipoproteins(HDL-c),low density lipoproteins(LDL-c), very low-density lipoproteins] was determined by spectrophotometry and standard formulas when applicable. RESULTS The T2D patient group showed significantly higher values of waist circumference, waist-to-hip ratio, systolic blood pressure(SBP), diastolic blood pressure(DBP),current smoking, and alcohol use when compared to the HS group(P < 0.05). We observed a significantly lower serum ucO C concentration in T2D than in HS(1.5 ± 1.4vs 2.3 ± 1.8, P < 0.05). In the whole study population,ucO C concentration was inversely correlated with body mass index(BMI)(r =-0.236, P < 0.05), fasting plasma glucose(r =-0.283, P < 0.01) and HDL-c(r =-0.255,P < 0.05); and positively correlated with LDL-c/HDL-c ratio(r = 0.306, P < 0.05) and TC/HDL-c ratio(r =0.284, P < 0.05). In the T2D group, serum uc OC concentration was inversely correlated with BMI(r =-0.310, P < 0.05) and body-fat percentage(r =-0.311,P < 0.05), and positively correlated with DBP(r = 0.450,P < 0.01). In HS group a positive correlation between serum levels of uc OC and SBP(r = 0.277, P < 0.05)was observed. CONCLUSION Serum uc OC is a potential marker for cardiovascular risk in Mexicans because it is related to adiposity parameters, blood pressure and lipid profile.展开更多
BACKGROUND Uncarboxylated osteocalcin(GluOC)has been reported to improve glucose metabolism,prevent type 2 diabetes,and decrease the severity of obesity in mice with type 2 diabetes.GluOC can increase glucose uptake i...BACKGROUND Uncarboxylated osteocalcin(GluOC)has been reported to improve glucose metabolism,prevent type 2 diabetes,and decrease the severity of obesity in mice with type 2 diabetes.GluOC can increase glucose uptake in a variety of cells.Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation.We hypothesized that decarboxylated osteocalcin(dcOC),a kind of GluOC,can increase glucose uptake in MG63 cells(osteoblast-like osteosarcoma cells)and influence their proliferation and differentiation.AIM To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved.METHODS MG63 cells(human osteoblast-like osteosarcoma cells)were treated with dcOC(0,0.3,3,10,or 30 ng/mL)for 1 and 72 h,and glucose uptake was measured by flow cytometry.The effect of dcOC on cell proliferation was measured with a CCK-8 assay,and alkaline phosphatase(ALP)enzyme activity was measured.PI3K was inhibited with LY294002,and hypoxia-inducible factor 1 alpha(HIF-1α)was silenced with siRNA.Then,GPRC6A(G protein-coupled receptor family C group 6 subtype A),total Akt,phosphorylated Akt,HIF-1α,and glucose transporter 1(GLUT1)levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake.RESULTS The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term(1 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term(72 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).DcOC triggered Akt phosphorylation in a dose-dependent manner,and the most effective stimulatory concentration of dcOC for short-term(1 h)was 3 ng/mL(P<0.01).LY294002 abolished the dcOC-mediated(1 h)promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression.Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α,GLUT1,and Runx2 in a dose-dependent manner.Inhibition of HIF-1αwith siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression.DcOC interven-tion promoted cell proliferation in a time-and dose-dependent manner as determined by the CCK-8 assay.Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h(P<0.01).CONCLUSION Short-and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells.This effect may occur through the PI3K/Akt,HIF-1α,and GLUT1 signaling factors.展开更多
After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. La...After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. Laser scanning confocal detection showed that fl-TCP ceramics could increase the mineralization level of osteoblast. Furthermore, RT-PCR showed that fl-TCP could increase the expression level of osteocalcin. Those results indicate β-TCP ceramics had perfect biocompatibility and increased the mineralization of osteoblast to accelerate osteogenesis by means of affecting the expression of genes involving in osteogeneticprocess.展开更多
In conditions of corticosteroid excess, such as Cushing’s syndrome, a reduction in serum osteocalcin is observed and bone loss occurs. The human osteocalcin gene is induced by 1,25-dihydroxyvitamin D3 derivatives and...In conditions of corticosteroid excess, such as Cushing’s syndrome, a reduction in serum osteocalcin is observed and bone loss occurs. The human osteocalcin gene is induced by 1,25-dihydroxyvitamin D3 derivatives and repressed by glucocorticoids. In this paper we show that cortisol, a natural glucocorticoid, represses both basal and vitamin D induced activity of the human osteocalcin promoter. Furthermore, we address the specific question as to whether the anti-progestin anti-glucocorticoid RU486 is able to antagonize the inhibitory effect of cortisol on osteocalcin gene expression. We show that RU486 has agonist activity alone, in that it is able to repress the basal promoter activity of the osteocalcin gene and antagonist activity, reversing incompletely the cortisol mediated repression of 1,25-dihydroxyvitamin D3 induction.展开更多
Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study ...Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study the effect on bone mineral density （BMD） and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients, for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol. Methods： One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 rag/day （n = 50） or Anastrozole 10 mg （n = 50）. Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups. Results： Use of Tamoxifen was associated with significant annual decrease in osteocalcin （P = 0.001）, whereas Anastrozole group had gradual increase of the annual levels （P 〈 0.01）. BMD decreased significantly in Anastrozole versus Tamoxifen groups （2.6% vs. 0.4%, P 〈 0.001）. Osteoporosis T 〈 -2.5 was reported significantly higher in Anastrozole group （P 〈 0.01）. Women with initial osteopenia in Anastrozole group showed significant decrease in BMD （P 〈 0.05）. The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD. Conclusion： Tamoxifen preserves BMD in postmenopausal breast cancer patients, whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy, moreover, the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.展开更多
Objective: To study the relationship between serum osteocalcin level and glucose and lipid metabolism in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease. Methods: The clinical ...Objective: To study the relationship between serum osteocalcin level and glucose and lipid metabolism in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease. Methods: The clinical data of 180 type 2 diabetes mellitus patients in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China from February 2017 to January 2018 were retrospectively analyzed, including 90 cases of nonalcoholic fatty liver disease patients (group A) and 90 cases of nonalcoholic fatty liver disease-free patients (group B), meanwhile another 100 healthy subjects were selected as the control group. Then various indexes were compared between groups, including serum osteocalcin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), prothrombin activity (PTA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting insulin (FINS), fasting C peptide (FCP), HOMA insulin resistance index (HOMA-IR), HOMA β-cell function (HOMA-β). Results: The serum osteocalcin and PTA in group A were significantly lower than those in group B and the control group (P<0.05). ALT, AST, and ALP were significantly higher than those in group B and the control group (P<0.05). The FBG and HbA1c in group A were significantly higher than those in group B and the control group (P<0.05). The TG, TC, LDL, and HDL of group A and group B were significantly higher than those of the control group (P<0.05). The FINS, FCP, and HOMA-IR in group A were significantly higher than those in group B and the control group (P<0.05). HOMA-βwas significantly lower than group B and the control group (P<0.05). Pearson correlation analysis showed that the serum osteocalcin was not correlated with ALT, AST, ALP, PTA, HbA1c, TG, TC, LDL, HDL and FINS (P>0.05), but negatively correlated with FBG and HOMA-IR (P<0.05), and positively correlated with FCP and HOMA-β (P<0.05). With serum osteocalcin as the dependent variable, and ALT, AST, ALP, PTA, FBG, HbA1c, TG, TC, LDL, HDL, FINS, FCP, HOMA-IR and HOMA-β as independent variables, multiple stepwise regression analysis showed that the FBG, HOMA-IR and HOMA-β were independent risk factors for osteocalcin. Conclusions: Patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease have lower serum osteocalcin level, which is susceptible to FBG, HOMA-IR, HOMA-β, and other factors.展开更多
Osteocalcin(OCN),a non-collagenous protein synthesized by osteoblasts,is integral to bone mineralization and demonstrates significant effects on metabolic and neurological functions.Its undercarboxylated form,Glu-OCN,...Osteocalcin(OCN),a non-collagenous protein synthesized by osteoblasts,is integral to bone mineralization and demonstrates significant effects on metabolic and neurological functions.Its undercarboxylated form,Glu-OCN,has emerged as a key regulator of glucose metabolism in diabetes,bone density in osteoporosis(OP),and lipid metabolism in conditions such as nonalcoholic fatty liver disease(NAFLD).Additionally,Glu-OCN is implicated in neurodegenerative and cardiovascular diseases through its roles in neurotransmitter synthesis and vascular calcification,respectively.This review examines the essential functions of Glu-OCN in the management of metabolic and neurodegenerative disorders,emphasizing its significance as both a diagnostic biomarker and therapeutic target.While findings to date are promising,most studies remain observational.Advanced detection methodologies and extensive longitudinal studies are urgently needed to elucidate the mechanisms and clinical applications of Glu-OCN.Advancements in this area could facilitate the integration of Glu-OCN into personalized medicine approaches,improving early diagnosis,risk assessment,and treatment monitoring.展开更多
Objective This study aimed to investigate possible serum 25-hydroxyvitamin D[25(OH)D]cutoffs for the associations between 25(OH)D and Bone turnover markers(BTMs),and how GC gene variation influences such cutoffs in Ch...Objective This study aimed to investigate possible serum 25-hydroxyvitamin D[25(OH)D]cutoffs for the associations between 25(OH)D and Bone turnover markers(BTMs),and how GC gene variation influences such cutoffs in Chinese women of childbearing age.Methods In total,1,505 non-pregnant or non-lactating women(18–45 years)were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance.Serum 25(OH)D,osteocalcin(OC),procollagen type 1 N-terminal propeptide(P1NP),β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide(β-CTX),and single nucleotide polymorphisms were determined.Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.Results The median serum 25(OH)D was 16.63(11.96–22.55)ng/mL and the prevalence of low serum 25(OH)D(<12 ng/mL)was 25.2%.Women with the lowest 25(OH)D had the highestβ-CTX.After adjustment for the confounders,25(OH)D cutoffs for OC[14.04(12.84–15.23)ng/mL],β-CTX[13.94(12.49–15.39)ng/mL],and P1NP[13.87(12.37–15.37)ng/mL]in the whole population,cutoffs for OC[12.30(10.68–13.91)ng/mL],β-CTX[12.23(10.22–14.23)ng/mL],and P1NP[11.85(10.40–13.31)ng/mL]in women with the GC rs2282679 G allele,and cutoffs for OC[12.75(11.81–13.68)ng/mL],β-CTX[13.05(11.78–14.32)ng/mL],and P1NP[12.81(11.57–14.06)ng/mL]in women with the GC rs2282679 T allele,were observed.Below these cutoffs,BTMs were negatively associated with 25(OH)D,while above these cutoffs,BTMs plateaued.Conclusion In Chinese women of childbearing age,there were thresholds effect of serum 25(OH)D concentrations on BTMs.The results indicated that serum 25(OH)D concentrations<13.87 ng/mL in this population had adverse influences on maintaining bone remodeling.BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.展开更多
基金supported by grant (81771036) from National Natural Science Foundation of China (to S.G.S.)grant (81741028) from National Natural Science Foundation of China (to J.D.)grant (17410710500) Shanghai International Scientific and Technological Cooperation Projects Laser Micromachine and Vascularization of TCP/PCL Scaffolds (to W.Z.)
文摘Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues.The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells.Initially,we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells.Moreover,Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line.In addition,micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo.Unexpectedly,Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2,Dlx5,Msx2,and Osterix,but led to upregulation of Alp and Osteocalcin (OCN),both of which play critical roles in promoting osteoblast maturation.Importantly,luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity.Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis,we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes.Based on these findings,we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene,suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.
文摘The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.
文摘AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study was conducted on 140 subjects classified into two groups, 70 with T2D and 70 HS. Medical history and physical examination with anthropometric measurements were obtained from all subjects. Body fat percentage was determined by bioelectrical impendency analysis. Serum uc OC concentration was determined by enzyme immunoassay,while serum levels of insulin and hsC RP were obtained using high sensitivity enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment-IR. Lipid profile [triglycerides,total cholesterol(TC), high-density lipoproteins(HDL-c),low density lipoproteins(LDL-c), very low-density lipoproteins] was determined by spectrophotometry and standard formulas when applicable. RESULTS The T2D patient group showed significantly higher values of waist circumference, waist-to-hip ratio, systolic blood pressure(SBP), diastolic blood pressure(DBP),current smoking, and alcohol use when compared to the HS group(P < 0.05). We observed a significantly lower serum ucO C concentration in T2D than in HS(1.5 ± 1.4vs 2.3 ± 1.8, P < 0.05). In the whole study population,ucO C concentration was inversely correlated with body mass index(BMI)(r =-0.236, P < 0.05), fasting plasma glucose(r =-0.283, P < 0.01) and HDL-c(r =-0.255,P < 0.05); and positively correlated with LDL-c/HDL-c ratio(r = 0.306, P < 0.05) and TC/HDL-c ratio(r =0.284, P < 0.05). In the T2D group, serum uc OC concentration was inversely correlated with BMI(r =-0.310, P < 0.05) and body-fat percentage(r =-0.311,P < 0.05), and positively correlated with DBP(r = 0.450,P < 0.01). In HS group a positive correlation between serum levels of uc OC and SBP(r = 0.277, P < 0.05)was observed. CONCLUSION Serum uc OC is a potential marker for cardiovascular risk in Mexicans because it is related to adiposity parameters, blood pressure and lipid profile.
基金Supported by Provincial Science and Technology Department Natural Fund Guidance Project,No.2019-ZD-0774National Natural Science Foundation of China,No.81470998+1 种基金Liaoning Ministry of Education,No.LQNK201715and Liaoning Provincial Doctor Start up Fund,No.20180540008.
文摘BACKGROUND Uncarboxylated osteocalcin(GluOC)has been reported to improve glucose metabolism,prevent type 2 diabetes,and decrease the severity of obesity in mice with type 2 diabetes.GluOC can increase glucose uptake in a variety of cells.Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation.We hypothesized that decarboxylated osteocalcin(dcOC),a kind of GluOC,can increase glucose uptake in MG63 cells(osteoblast-like osteosarcoma cells)and influence their proliferation and differentiation.AIM To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved.METHODS MG63 cells(human osteoblast-like osteosarcoma cells)were treated with dcOC(0,0.3,3,10,or 30 ng/mL)for 1 and 72 h,and glucose uptake was measured by flow cytometry.The effect of dcOC on cell proliferation was measured with a CCK-8 assay,and alkaline phosphatase(ALP)enzyme activity was measured.PI3K was inhibited with LY294002,and hypoxia-inducible factor 1 alpha(HIF-1α)was silenced with siRNA.Then,GPRC6A(G protein-coupled receptor family C group 6 subtype A),total Akt,phosphorylated Akt,HIF-1α,and glucose transporter 1(GLUT1)levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake.RESULTS The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term(1 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term(72 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).DcOC triggered Akt phosphorylation in a dose-dependent manner,and the most effective stimulatory concentration of dcOC for short-term(1 h)was 3 ng/mL(P<0.01).LY294002 abolished the dcOC-mediated(1 h)promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression.Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α,GLUT1,and Runx2 in a dose-dependent manner.Inhibition of HIF-1αwith siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression.DcOC interven-tion promoted cell proliferation in a time-and dose-dependent manner as determined by the CCK-8 assay.Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h(P<0.01).CONCLUSION Short-and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells.This effect may occur through the PI3K/Akt,HIF-1α,and GLUT1 signaling factors.
基金the Research Fund of Key Labortary for Advanced Technology in Environmental Protection of Jiangsu Province (No. AE201037)the Foundation for Talent Recruitment of Yancheng Institute of Technology (No. XKR2011007)the "973" Chinese National Key Fundamental Research and Development Program (No. G1999064701)
文摘After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. Laser scanning confocal detection showed that fl-TCP ceramics could increase the mineralization level of osteoblast. Furthermore, RT-PCR showed that fl-TCP could increase the expression level of osteocalcin. Those results indicate β-TCP ceramics had perfect biocompatibility and increased the mineralization of osteoblast to accelerate osteogenesis by means of affecting the expression of genes involving in osteogeneticprocess.
文摘In conditions of corticosteroid excess, such as Cushing’s syndrome, a reduction in serum osteocalcin is observed and bone loss occurs. The human osteocalcin gene is induced by 1,25-dihydroxyvitamin D3 derivatives and repressed by glucocorticoids. In this paper we show that cortisol, a natural glucocorticoid, represses both basal and vitamin D induced activity of the human osteocalcin promoter. Furthermore, we address the specific question as to whether the anti-progestin anti-glucocorticoid RU486 is able to antagonize the inhibitory effect of cortisol on osteocalcin gene expression. We show that RU486 has agonist activity alone, in that it is able to repress the basal promoter activity of the osteocalcin gene and antagonist activity, reversing incompletely the cortisol mediated repression of 1,25-dihydroxyvitamin D3 induction.
文摘Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study the effect on bone mineral density （BMD） and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients, for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol. Methods： One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 rag/day （n = 50） or Anastrozole 10 mg （n = 50）. Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups. Results： Use of Tamoxifen was associated with significant annual decrease in osteocalcin （P = 0.001）, whereas Anastrozole group had gradual increase of the annual levels （P 〈 0.01）. BMD decreased significantly in Anastrozole versus Tamoxifen groups （2.6% vs. 0.4%, P 〈 0.001）. Osteoporosis T 〈 -2.5 was reported significantly higher in Anastrozole group （P 〈 0.01）. Women with initial osteopenia in Anastrozole group showed significant decrease in BMD （P 〈 0.05）. The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD. Conclusion： Tamoxifen preserves BMD in postmenopausal breast cancer patients, whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy, moreover, the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.
文摘Objective: To study the relationship between serum osteocalcin level and glucose and lipid metabolism in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease. Methods: The clinical data of 180 type 2 diabetes mellitus patients in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China from February 2017 to January 2018 were retrospectively analyzed, including 90 cases of nonalcoholic fatty liver disease patients (group A) and 90 cases of nonalcoholic fatty liver disease-free patients (group B), meanwhile another 100 healthy subjects were selected as the control group. Then various indexes were compared between groups, including serum osteocalcin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), prothrombin activity (PTA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting insulin (FINS), fasting C peptide (FCP), HOMA insulin resistance index (HOMA-IR), HOMA β-cell function (HOMA-β). Results: The serum osteocalcin and PTA in group A were significantly lower than those in group B and the control group (P<0.05). ALT, AST, and ALP were significantly higher than those in group B and the control group (P<0.05). The FBG and HbA1c in group A were significantly higher than those in group B and the control group (P<0.05). The TG, TC, LDL, and HDL of group A and group B were significantly higher than those of the control group (P<0.05). The FINS, FCP, and HOMA-IR in group A were significantly higher than those in group B and the control group (P<0.05). HOMA-βwas significantly lower than group B and the control group (P<0.05). Pearson correlation analysis showed that the serum osteocalcin was not correlated with ALT, AST, ALP, PTA, HbA1c, TG, TC, LDL, HDL and FINS (P>0.05), but negatively correlated with FBG and HOMA-IR (P<0.05), and positively correlated with FCP and HOMA-β (P<0.05). With serum osteocalcin as the dependent variable, and ALT, AST, ALP, PTA, FBG, HbA1c, TG, TC, LDL, HDL, FINS, FCP, HOMA-IR and HOMA-β as independent variables, multiple stepwise regression analysis showed that the FBG, HOMA-IR and HOMA-β were independent risk factors for osteocalcin. Conclusions: Patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease have lower serum osteocalcin level, which is susceptible to FBG, HOMA-IR, HOMA-β, and other factors.
文摘Osteocalcin(OCN),a non-collagenous protein synthesized by osteoblasts,is integral to bone mineralization and demonstrates significant effects on metabolic and neurological functions.Its undercarboxylated form,Glu-OCN,has emerged as a key regulator of glucose metabolism in diabetes,bone density in osteoporosis(OP),and lipid metabolism in conditions such as nonalcoholic fatty liver disease(NAFLD).Additionally,Glu-OCN is implicated in neurodegenerative and cardiovascular diseases through its roles in neurotransmitter synthesis and vascular calcification,respectively.This review examines the essential functions of Glu-OCN in the management of metabolic and neurodegenerative disorders,emphasizing its significance as both a diagnostic biomarker and therapeutic target.While findings to date are promising,most studies remain observational.Advanced detection methodologies and extensive longitudinal studies are urgently needed to elucidate the mechanisms and clinical applications of Glu-OCN.Advancements in this area could facilitate the integration of Glu-OCN into personalized medicine approaches,improving early diagnosis,risk assessment,and treatment monitoring.
基金funded by the National Natural Science Foundation of China(No.81872627and No.82473611)the National Financial Projects ‘Assessment and Application of Nutrients Requirement and Food Environment for Chinese Residents’(No.102393220020070000013)。
文摘Objective This study aimed to investigate possible serum 25-hydroxyvitamin D[25(OH)D]cutoffs for the associations between 25(OH)D and Bone turnover markers(BTMs),and how GC gene variation influences such cutoffs in Chinese women of childbearing age.Methods In total,1,505 non-pregnant or non-lactating women(18–45 years)were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance.Serum 25(OH)D,osteocalcin(OC),procollagen type 1 N-terminal propeptide(P1NP),β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide(β-CTX),and single nucleotide polymorphisms were determined.Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.Results The median serum 25(OH)D was 16.63(11.96–22.55)ng/mL and the prevalence of low serum 25(OH)D(<12 ng/mL)was 25.2%.Women with the lowest 25(OH)D had the highestβ-CTX.After adjustment for the confounders,25(OH)D cutoffs for OC[14.04(12.84–15.23)ng/mL],β-CTX[13.94(12.49–15.39)ng/mL],and P1NP[13.87(12.37–15.37)ng/mL]in the whole population,cutoffs for OC[12.30(10.68–13.91)ng/mL],β-CTX[12.23(10.22–14.23)ng/mL],and P1NP[11.85(10.40–13.31)ng/mL]in women with the GC rs2282679 G allele,and cutoffs for OC[12.75(11.81–13.68)ng/mL],β-CTX[13.05(11.78–14.32)ng/mL],and P1NP[12.81(11.57–14.06)ng/mL]in women with the GC rs2282679 T allele,were observed.Below these cutoffs,BTMs were negatively associated with 25(OH)D,while above these cutoffs,BTMs plateaued.Conclusion In Chinese women of childbearing age,there were thresholds effect of serum 25(OH)D concentrations on BTMs.The results indicated that serum 25(OH)D concentrations<13.87 ng/mL in this population had adverse influences on maintaining bone remodeling.BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
