Overexpression of Dlx2 enhances osteogenic differentiation of BMSCs and MC3T3-E1 cells via direct upregulation of Osteocalcin and Alp

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.

Osteocalcin as a hormone regulating glucose metabolism

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.

Serum levels of undercarboxylated osteocalcin are related to cardiovascular risk factors in patients with type 2 diabetes mellitus and healthy subjects

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.

Decarboxylated osteocalcin,a possible drug for type 2 diabetes,triggers glucose uptake in MG63 cells

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.

Effects of β-TCP Ceramics on Osteoblast Cellular Proliferating,Mineralization and Osteocalcin Expression

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.

RU486 Reversal of Cortisol Repression of 1,25-Dihydroxyvitamin D₃Induction of the Human Osteocalcin Promoter

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.

Skeletal events of Anastrozole versus Tamoxifen on bone mineral density and bone biomarker osteocalcin in postmenopausal women with early breast cancer

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.

Relationship between serum osteocalcin level and glucose and lipid metabolism in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease

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.

哈蟆油蛋白对骨质疏松预防及ALP,Osteocalcin,Runx-2基因表达的调节作用

目的:观察哈蟆油蛋白(ROP)的抗骨质疏松作用,并探讨其对骨生长相关基因的调节作用。方法:采用去势法建立大鼠骨质疏松模型,随机分为空白组,模型组,戊酸雌二醇组,ROP高、中、低剂量组(0.15,0.075,0.037 5 g·kg^(-1));利用X射线技术测量股骨和腰椎骨密度(BMD);利用骨骼强度仪检测股骨的最大载荷量;应用实时荧光定量PCR(Real-time PCR)技术检测骨生长相关基因的表达。结果:与空白组比较,模型组股骨、腰椎骨密度明显降低(P<0.05,P<0.01),碱性磷酸酶(alkaline phosphatase,ALP),Osteocalcin,Runx-2基因表达均显著下调(P<0.01);与模型组比较,ROP高、中剂量组腰椎BMD均有显著增加(P<0.01),ROP高剂量组ALP,Osteocalcin,Runx-2基因表达显著上调(P<0.01)。结论:ROP能显著提高大鼠BMD和最大载荷量;ROP可能通过上调ALP,Osteocalcin,Runx-2基因的mRNA表达,促进成骨分化,调节骨代谢平衡,从而发挥防治骨质疏松的作用。

外敷温经药酒联合针刺对骨质疏松大鼠的影响

目的探究外敷温经药酒联合针刺对骨质疏松大鼠的影响。方法选取SPF级雌性大鼠40只,分为正常组、模型组、针刺组、联合组,每组10只。除正常组外其余均建立骨质疏松(osteoporosis,OP)大鼠模型。建模成功后正常组、模型组不予处理,针刺组入穴关元、三阴交(双)、肾俞(双)、后三里(双)后连接电针仪治疗,5 d/周,每日一次,20 min/次,共12周。联合组在针刺治疗基础上外敷温经药酒,每日两次,共12周。用ELISA法检测血清中骨钙素(OC)、吡啶酚(PYD)、Ⅰ型前胶原羧基端肽(PICP)水平;用计算机断层扫描检测骨小梁厚度(Tb.Th)、骨小梁间隔(Tb.Sp)、骨密度(bone mineral density,BMD)、皮质骨面积(Ct.Ar);运用TUNEL法检测成骨细胞凋亡;通过HE染色观察股骨组织病理改变;通过Western blot法测Notch1、Notch2、Jagged1、Jagged2。结果与正常组比较,模型组PYD、Tb.Sp、成骨细胞凋亡率升高,OC、PICP、Tb.Th、BMD、Ct.A、Notch1、Notch2、Jagged1、Jagged2降低(P<0.05);与模型组比较,针刺组PYD、Tb.Sp、成骨细胞凋亡率降低,OC、PICP、Tb.Th、BMD、Ct.A、Notch1、Notch2、Jagged1、Jagged2升高(P<0.05);与针刺组比较,联合组PYD、Tb.Sp、成骨细胞凋亡率降低,OC、PICP、Tb.Th、BMD、Ct.A、Notch1、Notch2、Jagged1、Jagged2升高(P<0.05);正常组大鼠骨形态结构良好;模型组骨损伤严重;针刺组与联合组骨形态结构有所改善,其中联合组改善更为良好。结论外敷温经药酒联合针刺对骨质疏松大鼠的骨钙素、成骨细胞活性及Notch信号通路等的改善作用良好,建议推广使用。

血清骨钙素及SIRT6在急性缺血性脑卒中的表达及预后价值分析

目的分析急性缺血性脑卒中(AIS)患者血清骨钙素、去乙酰化酶6(SIRT6)表达及其对临床预后的评估价值。方法收集2019年2月—2021年2月重庆市巴南区人民医院神经内科诊治AIS患者90例为AIS组,以同期诊治的高血压或糖尿病患者90例为非AIS组,以同期体检的健康人90例为健康对照组。随访3个月,根据AIS患者预后分为预后不良亚组(n=24)和预后良好亚组(n=66)。利用酶联免疫吸附试验检测血清骨钙素及SIRT6水平。分析AIS患者预后影响因素及血清骨钙素、SIRT6对AIS患者预后评估价值。结果与健康对照组比较,AIS组血清骨钙素、SIRT6水平显著降低(t/P=25.013/<0.001、27.571/<0.001),与非AIS组比较,AIS组显著降低(t/P=31.808/<0.001、36.440/<0.001),健康对照组及非AIS组比较差异无统计学意义(t/P=2.559/0.152、3.113/0.067);重症亚组、中症亚组及轻症亚组AIS患者血清骨钙素及SIRT6依次降低(F/P=15.234/<0.001、30.388/<0.001)。与预后良好亚组比较,预后不良亚组AIS患者梗死面积大、NIHSS评分较高,血清骨钙素及SIRT6较低(χ^(2)/t=8.511、22.826、3.592、3.729,P均<0.001);梗死面积大、NIHSS评分高是影响AIS患者不良预后的独立危险因素[OR(95%CI)=1.397(1.141~1.709)、1.363(1.076~1.728)],血清骨钙素及SIRT6高是影响AIS患者不良预后的独立保护因素[OR(95%CI)=0.770(0.610~0.973)、0.709(0.549~0.915)]。血清骨钙素、SIRT6及两项联合对AIS患者不良预后预测的AUC分别为0.782、0.796、0.886,两项联合的AUC大于各自单独预测效能(Z=4.526、4.209,P均<0.001)。结论AIS患者血清骨钙素、SIRT6降低,两者与AIS病情严重程度有关,可作为评估AIS患者预后的血清生物标志物。

血清BGP、miR-17-92、sST2与CHD患者PCI术后预后的关系

目的探讨骨钙素(BGP)、微小RNA-17-92a(miR-17-92)可溶性生长刺激表达基因2蛋白(sST2)与冠心病(CHD)患者经皮冠状动脉介入(PCI)术后预后的关系。方法选取2020年6月至2022年6月南阳市第一人民医院收治并行PCI术的168例CHD患者作为研究组,另选取同期53例未行PCI的CHD患者作为对照组。比较两组患者的血清BGP、miR-17-92、sST2水平,研究组患者随访12个月,失访6例,依据预后情况分为预后不良组126例和预后良好组36例,采用多因素Logistic回归分析影响CHD患者PCI术后预后的危险因素;绘制受试者工作特征(ROC)曲线分析血清BGP、miR-17-92、s ST2对预后不良的预测效能。结果两组患者的血清BGP比较差异无统计学意义(P>0.05),但研究组患者的血清miR-17-92、sST2分别为1.55±0.29、(53.48±10.84)ng/mL,明显高于对照组的1.41±0.30、(20.64±5.97)ng/mL,差异均有统计学意义(P<0.05);预后不良组患者的miR-17-92、s ST2分别为1.59±0.29、(58.33±8.43)ng/mL,明显高于预后良好组的1.45±0.28、(52.15±6.86)ng/mL,而血清BGP水平为(23.06±3.84)ng/mL,明显低于预后良好组的(27.19±4.31)ng/mL,差异均有统计学意义(P<0.05);多因素Logistic回归分析结果显示,miR-17-92、sST2是CHD患者PCI术后预后的独立危险因素,而血清BGP是保护因素(P<0.05);ROC曲线分析结果显示,血清BGP、miR-17-92、s ST2单独及联合检测预测CHD患者PCI术后预后的曲线下面积(AUC)分别为0.783、0.628、0.723、0.856,联合预测的AUC明显高于单独预测(Z=2.897、4.627、1.984,P<0.05)。结论血清miR-17-92、sST2均是CHD患者PCI术后预后的危险因素,BGP是保护因素,监测其变化对CHD患者PCI术后预后有一定预测价值。

2型糖尿病病人外周血羧化不全骨钙素水平与合并非酒精性脂肪性肝病的关系分析

目的检测2型糖尿病(T2DM)病人羧化不全骨钙素(ucOC)浓度,并分析其与合并非酒精性脂肪性肝病(NAFLD)的关系。方法选取石家庄市第二医院2020年6月至2022年6月收治的234例T2DM病人设为疾病组,根据病人是否合并NAFLD分为NAFLD组(107例)和非NAFLD组(127例),同期选取231例健康体检者为对照组,采用酶联免疫吸附测定检测受试者外周血ucOC浓度。比较NAFLD组和非NAFLD组病人的临床资料,采用多因素logistic回归分析法分析T2DM病人合并NAFLD的影响因素,并绘制受试者操作特征曲线(ROC曲线)评价外周血ucOC浓度对T2DM合并NAFLD的诊断价值。结果疾病组外周血ucOC浓度[(1.10±0.42)μg/L]低于对照组[(1.53±0.68)μg/L](P<0.05);NAFLD组ucOC[(0.98±0.14)μg/L]低于非NAFLD组[(1.20±0.21)μg/L](P<0.05)。NAFLD组身体质量指数(BMI)、腰臀比以及空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、舒张压、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、尿酸、胰岛素抵抗指数(HOMA-IR)均高于非NAFLD组(P<0.05),高密度脂蛋白(HDL-C)低于非NAFLD组(P<0.05)。多因素结果显示,HbA1c、TG、尿酸及HOMA-IR升高均是T2DM病人合并NAFLD的危险因素(P<0.05),外周血ucOC浓度升高是其保护因素(P<0.05)。外周血ucOC浓度诊断T2DM病人合并NAFLD的最佳截断值、灵敏度、特异度、曲线下面积分别为1.05μg/L、83.18%、80.31%、0.84。结论T2DM病人外周血ucOC浓度降低,且合并NAFLD病人外周血ucOC浓度低于未合并病人。ucOC浓度与HbA1c、TG、尿酸、HOMA-IR均是T2DM病人合并NAFLD的影响因素,监测T2DM病人ucOC浓度变化有助于临床诊断NAFLD的发生。

基于PI3K/Akt/mTOR信号通路、性激素、骨代谢探究知柏地黄丸联合治疗女性特发性性早熟的效果及机制

目的探讨联合知柏地黄丸对女性特发性性早熟(CPP)患儿性激素、骨代谢及PI3K/Akt/mTOR信号通路的影响。方法选取2022年1月—2022年12月收治的60例CPP患儿,随机数字表法分为西药组、联合组2组,均30例。西药组给予注射用曲普瑞林治疗,联合组在西药组基础上联合知柏地黄丸治疗。比较2组临床疗效、安全性,以及治疗前后子宫体积、卵巢体积、卵泡直径、性激素水平[促黄体生成素(LH)、LH/促卵泡激素(FSH)、雌二醇(E_(2))]、骨代谢指标[骨钙素、骨碱性磷酸酶(BALP)、Ⅰ型前胶原氨基端肽(PⅠNP)、骨密度、β-胶原降解产物(β-CTX)]、PI3K/Akt/mTOR信号通路相关蛋白表达。结果联合组总有效率96.67%(29/30)高于西药组70.00%(21/30)(P<0.05)。联合组治疗后子宫体积、卵巢体积、卵泡直径均低于西药组(P<0.05);联合组治疗后血清LH、LH/FSH、E_(2)、骨钙素、BALP、PⅠNP水平低于西药组,骨密度高于西药组(P<0.05)。2组治疗后血清β-CTX水平比较无显著差异(P>0.05)。联合组治疗后PI3K、Akt、mTOR蛋白表达水平低于西药组(P<0.05)。联合组不良反应总发生率与西药组比较无显著差异(P>0.05)。结论注射用曲普瑞林联合知柏地黄丸能降低CPP患儿性激素水平,改善骨代谢相关因子的表达,抑制PI3K/Akt/mTOR信号通路活性,从而改善患儿症状。研究结果表明该方案临床疗效确切,且具有一定安全性。

血清BALP、BGP、β-CTx联合FRAX预测绝经后骨质疏松症患者髋部骨折风险的价值

目的探讨血清骨碱性磷酸酶(BALP)、骨钙素(BGP)、β-Ⅰ型胶原羧基端肽(β-CTx)联合骨折风险评估工具(FRAX)预测绝经后骨质疏松症髋部骨折风险的价值。方法选取2020年1月至2022年12月该院收治的绝经后骨质疏松症患者132例纳入骨质疏松组,另选择同期在该院诊断为骨量下降的123例和骨量正常的120例绝经后女性分别纳入骨量下降组和对照组。比较各组血清BALP、BGP、β-CTx水平及FRAX检测的髋部骨折风险。对绝经后骨质疏松症患者进行4~36个月的随访,根据骨质疏松症患者髋部是否骨折将其分为骨折组和未骨折组。采用多因素Logistic回归分析绝经后骨质疏松症患者髋部骨折的影响因素,绘制受试者工作特征(ROC)曲线分析血清BALP、BGP、β-CTx与FRAX单独及联合对绝经后骨质疏松症患者髋部骨折的预测价值。结果骨质疏松组血清BALP、BGP、β-CTx水平和FRAX检测的髋部骨折风险均高于骨量下降组和对照组,差异有统计学意义(P<0.05),骨量下降组血清BALP、BGP、β-CTx水平和FRAX检测的髋部骨折风险均高于对照组,差异有统计学意义(P<0.05)。132例绝经后骨质疏松症患者随访过程中,共有44例发生髋部骨折,发生率为33.33%。骨折组BALP、BGP、β-CTx水平和FRAX检测的髋部骨折风险均高于未骨折组,差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,父母有髋部骨折史,有脆性骨折史、长期糖皮质激素治疗史、类风湿关节炎史,无规律补钙、缺乏阳光照射及血清BALP、BGP、β-CTx水平升高均是绝经后骨质疏松症患者髋部骨折的危险因素(P<0.05),骨密度(BMD)升高、体育锻炼则是绝经后骨质疏松症患者髋部骨折的保护因素(P<0.05)。ROC曲线分析结果显示,血清BALP、BGP、β-CTx联合FRAX预测绝经后骨质疏松症患者髋部骨折的灵敏度、曲线下面积(AUC)分别为95.45%、0.954,均高于单独预测(P<0.05)。结论血清BALP、BGP、β-CTx及FRAX均对绝经后骨质疏松症患者髋部骨折发生风险具有一定的预测价值,且4项指标或方法联合检测的预测价值更高。

不同运动对男青年BMD、肌肉适能和肌骨共调节因子的影响

目的比较8周抗阻联合高强度间歇同期训练、单独高强度间歇训练和单独抗阻训练对男青年骨密度、肌肉适能以及血清肌骨共调节因子骨钙素和鸢尾素水平的影响。方法选取39名男青年,随机分为抗阻训练(RT)、高强度间歇训练(HIIT)和抗阻联合高强度间歇同期训练(CT)三组后,分别进行为期8周的运动干预。分别在干预前和干预后48 h测试受试者的骨密度(bone mineral density,BMD)、体成分、最大摄氧量、肌肉力量、爆发力以及血清骨钙素和鸢尾素水平。结果三种运动干预均能显著提高男青年的瘦体重,但只有HIIT(P<0.01)和CT干预(P<0.05)能显著降低男青年的体脂率;三种运动干预均能显著提高男青年的股骨BMD,但只有HIIT(P<0.05)和RT(P<0.05)干预能显著提高男青年的腰椎BMD;RT和CT干预能显著提升男青年的卧推、硬拉、划船、深蹲的最大力量(P<0.01)和反向纵跳高度(P<0.01),而HIIT干预只能显著提升深蹲的最大力量(P<0.01);三种运动干预均能显著提高男青年的血清鸢尾素和骨钙素水平。结论三种运动干预均能增加男青年的瘦体重、股骨BMD以及血清肌骨调节因子鸢尾素和骨钙素水平,但CT对腰椎BMD的提升效果小于HIIT和RT,而RT和CT对肌肉力量和爆发力的提升效果大于HIIT。

特发性矮小症儿童血清IGFBP-3、25(OH)D、Nesfatin-1和骨钙素水平及其临床意义

目的探讨特发性矮小症(ISS)儿童血清胰岛素生长因子结合蛋白-3(IGFBP-3)、25羟维生素D[25(OH)D]、摄食抑制因子-1(Nesfatin-1)、骨钙素水平及其临床意义。方法选取矮小症儿童286例为观察组,其中ISS组152例,生长激素缺乏(GHD)组134例;同时选取健康儿童100例为对照组。比较各组血清IGFBP-3、25(OH)D、Nesfatin-1、骨钙素水平差异,及其与体格发育等临床特征的关系。结果观察组儿童身高、骨龄指数、血清IGFBP-3、25(OH)D、骨钙素水平低于对照组,而Nesfatin-1高于对照组(P<0.05)。ISS组儿童身高、骨龄指数、血清IGFBP-3、25(OH)D、骨钙素水平高于GHD组,而Nesfatin-1低于GHD组(P<0.05)。血清IGFBP-3、25(OH)D和骨钙素水平身高≥125 cm儿童高于<125 cm儿童、骨龄指数≥0.90儿童高于<0.90儿童;而Nesfatin-1趋势相反(P<0.05)。ISS儿童血清IGFBP-3、25(OH)D、骨钙素与儿童身高、骨龄指数呈正相关(P<0.05),Nesfatin-1与儿童身高、骨龄指数呈负相关(P<0.05)。结论与健康儿童相比,ISS儿童血清IGFBP-3、25(OH)D、骨钙素水平较低,Nesfatin-1水平较高,可能与儿童体格发育存在相关性。

超重老年男性骨钙素与肌量的相关性研究

目的观察超重老年男性病人中,骨钙素与骨骼肌质量的相关性。方法收集2020—2022年南京鼓楼医院老年科收治的167例超重老年男性病人为研究对象,根据骨钙素水平分为低骨钙素组和正常骨钙素组,分析骨钙素与超重老年男性腰部肌量的相关性,并采用线性回归分析肌量的影响因素。结果2组间年龄、HbA1c、Ⅰ型胶原交联C末端肽(CTX)、Ⅰ型前胶原氨基端前肽(P1NP)、25-羟基维生素D、腰部肌量、髋部肌量差异均有统计学意义(P均<0.05)。骨钙素、CTX、P1NP均与髋部肌量及腰部肌量呈正相关(r=0.204~0.322,P均<0.05),年龄、BMI、腹围均与髋部肌量及腰部肌量呈负相关(r=-0.282~-0.187,P均<0.05)。多元线性回归分析显示,髋部肌量的独立影响因素为年龄、腹围(β=-0.081、-0.127,P均<0.05),腰部肌量的独立影响因素为年龄、腹围、骨钙素(β=-0.201、-0.136、0.187,P均<0.05)。结论超重老年男性病人腰部、髋部肌量与骨钙素呈正相关。骨钙素是腰部肌量的独立相关因素。

正畸牙移动过程中Piezo1通道对张力侧血管生成和成骨的影响

目的 探讨正畸牙移动过程中Piezo1通道对张力侧血管生成及成骨改建的影响,为加速正畸牙周组织改建提供实验依据。方法 本实验已获得单位实验动物伦理委员会批准。选取60只健康雄性SD大鼠以上颌双侧中切牙为支抗,使用镍钛拉簧施加0.5 N力近中移动大鼠上颌右侧第一磨牙构建正畸牙齿移动模型,随机分成3组,每组20只,加力后0、8 d时在右侧上颌第一磨牙颊、腭侧黏膜下分别注射等量生理盐水(对照组)、100μmol/L Piezo1通道激动剂(Yoda1组)、48μmol/L Piezo1通道抑制剂(GsMTx4组),分别在第1、3、7、14天测量牙齿移动距离并每组各处死5只大鼠,获取上颌组织标本。通过HE染色观察张力侧牙周组织病理生理变化,免疫组化染色标记张力侧血小板内皮细胞黏附分子(platelet endothelial cell adhesion molecule-1,PECAM-1/CD31)阳性细胞计数以进行微血管定量,检测张力侧骨钙素(osteocalcin,OCN)的表达情况。结果牙齿移动距离测量结果显示,Yoda1组第3、7、14天牙齿移动距离分别为(0.238±0.008)mm、(0.406±0.011)mm、(0.746±0.013)mm,与对照组相比显著增加(P<0.05);GsMTx4组第7、14天牙齿移动距离分别为(0.282±0.011)mm、(0.578±0.008)mm,与对照组相比显著减少(P<0.05)。HE染色结果显示,3组张力侧牙周膜间隙随加力时间增加逐渐增宽,其中对照组及Yoda1组加力第7天时可见成骨细胞,第14天时随后牙周膜间隙逐渐恢复到正常。CD31阳性细胞计数微血管定量分析结果显示,与对照组相比,Yoda1组第3天(8.027±0.225)、第7天(14.320±0.471)血管数量显著增多(P<0.05),在第7天达到峰值,随后逐渐下降;GsMTx4组加力第3天(6.013±0.177)、第7天(9.187±0.678)、第14天(12.613±0.334)张力侧牙周膜内血管数量增加显著减少(P<0.05)。免疫组化结果显示,与对照组相比,Yoda1组加力后各时间点OCN表达显著增强(P<0.05),GsMTx4组加力第7天、第14天的OCN表达减弱(P<0.05)。结论 Piezo1通道激活会促进正畸牙齿移动,促进张力侧血管生成及成骨改建,抑制Piezo1通道则产生相反的效果。

铅暴露对人群骨代谢影响的Meta分析

目的利用Meta分析的方法,研究铅暴露对人群骨代谢的影响。方法通过对中国期刊全文数据库、万方数据库、维普中文科技期刊数据库、PubMed、Web of science五个数据库,检索建库至2022年3月公开发表的铅暴露对人群骨代谢相关指标影响的文献,对文献进行筛选和资料提取。以AHRQ横断面研究评价标准对纳入文献进行质量评价。维生素D3、骨钙素、骨碱性磷酸酶作为骨代谢指标进行分析。采用Stata16、Review Manager 5.3软件进行森林图绘制、敏感性分析及发表偏倚检验,标准化均数差(SMD)及其95%可信区间(95%CI)作为效应指标。结果共纳入13篇文献(n=2029)。纳入的研究存在中高度异质性(I^(2)>50%),采取随机效应模型。相对于非铅接触人群,铅接触人群的钙磷代谢调节指标维生素D3的SMD为-1.11(95%CI:-2.20~-0.02),骨钙素的SMD为-0.50(95%CI:-0.91~-0.09),骨碱性磷酸酶的SMD为0.80(95%CI:0.42~1.19),差异均具有统计学意义(P<0.01)。结论Meta分析结果表明铅暴露影响人群的骨代谢,其中骨碱性磷酸酶水平升高,维生素D3、骨钙素水平下降。