激活素A和卵泡抑素对MG-63细胞株OCN、BMP-2蛋白表达的影响

目的 探讨激活素A (activin A)和卵泡抑素(follistatin,FS)对骨肉瘤细胞株(MG-63)骨钙素(osteocalcin,OCN)、骨形态形成蛋白-2(BMP-2)蛋白质表达的影响以及骨形成作用.方法 采用细胞培养结合Western blot检测,观察不同浓度激活素A以及加用卵泡抑素后对MG-63细胞OCN、BMP-2蛋白质表达的影响,并采用PNPP底物比色法检测MG-63细胞的碱性磷酸酶含量.结果 激活素A明显上调MG-63细胞OCN、BMP-2蛋白质表达(P＜0.05),随着激活素A剂量增加以及作用时间延长,OCN、BMP-2蛋白质表达量逐渐加大,并促进碱性磷酸酶的生成,但加用卵泡抑素后该作用得到抑制.结论 激活素A上调OCN、BMP-2蛋白质表达及促进骨形成,而卵泡抑素抑制该效应.     

中老年2型糖尿病患者血清骨钙素与 颈动脉粥样硬化病变的关系

ABSTRACT Objective To investigate the relationship between serum osteocalcin (OC) and carotid atherosclerosis (CAS) in middle-aged and elderly patients with T2DM. Methods A total of 430 middle-aged and elderly patients with T2DM were selected in the Department of Endocrinology in our hospital. Color Doppler ultrasound was used to detect the intima-media thickness (CIMT) of the bilateral carotid arteries, including 112 patients with normal CIMT (CIMT normal group), 106 patients with CIMT thickening (CIMT thickening group), and carotid atherosclerotic plaques There were 212 cases of lumps (CAS plaque group), and the differences in serum OC levels in each group were compared. Analyze the relationship between OC and CIMT thickening and the occurrence of CAS plaque. Results The mean OC in the CIMT thickening group (11.51±5.02) ng/ml and the mean OC in the CAS plaque group (11.59±4.23) ng/ml were significantly lower than the mean OC in the CIMT normal group (14.16±5.56) ng/ml, the difference was both There is statistical significance (P<0.01). Multivariate logistic regression analysis showed that the decrease of OC level is a risk factor for CIMT thickening and CAS plaque in middle-aged and elderly patients with T2DM. Conclusion Middle-aged and elderly T2DM patients with reduced OC levels are closely related to the risk of carotid atherosclerosis. Patients with significantly reduced OC levels should be reminded to undergo CAS screening early. KEY WORDS diabetes, type 2; middle-aged and elderly; osteocalcin; carotid artery intima-media thickness; atherosclerotic plaque     

Differentiation of Osteoblast in vitro Is Regulated by Progesterone

ＤｉｆｆｅｒｅｎｔｉａｔｉｏｎｏｆＯｓｔｅｏｂｌａｓｔｉｎｖｉｔｒｏＩｓＲｅｇｕｌａｔｅｄｂｙＰｒｏｇｅｓｔｅｒｏｎｅＣＨＥＮＬｕｌｕ（陈璐璐）（ＤｅｐａｒｔｍｅｎｔｏｆＥｎｄｏｃｒｉｎｏｌｏｇｙ，ＸｉｅｈｅＨｏｓｐｉｔａｌ，ＴｏｎｇｊｉＭｅｄｉｃａ...     

Verapamil increases serum ionized calcium and serum phosphate in patients with post-surgical hypoparathyroidism

The calcium homeostasis in eight patients with postoperative hypoparathyroidism was examined before and after 2 weeks of administration of verapamil in an oral dose of 80 mg three times daily. Serum ionized calcium increased during verapamil treatment (from mean +/- SD of 1.10 +/- 0.06 to 1.24 +/- 0.38 mmol l-1; P less than 0.05), as well as total serum calcium corrected for protein (from 2.11 +/- 0.13 to 2.18 +/- 0.13 mmol l-1; P less than 0.05). During treatment with verapamil there was an increase in serum phosphate (from 1.08 +/- 0.15 to 1.19 +/- 0.20 mmol l-1 P less than or equal to 0.05) and in the urinary excretion of phosphate (P/creatinine ratio from 1.22 +/- 0.69 to 1.83 +/- 0.97; P less than or equal to 0.05). The serum 1,25-dihydroxyvitamin-D3 and serum parathyroid hormone were below the detection limits both before and after verapamil treatment. There were no significant changes either of the intestinal absorption of calcium or of the urinary calcium excretion. Serum osteocalcin was insignificantly reduced after treatment (1.60 +/- 0.70 before treatment and 1.25 +/- 0.71 micrograms l-1 after treatment). Thus in patients with post-surgical hypoparathyroidism verapamil has effects on calcium and phosphorous homeostasis. Since calcium absorption was not influenced by verapamil, it is suggested that verapamil affects bone mineral metabolism.     

Age-Related Changes in Serum Undercarboxylated Osteocalcin and its Relationships with Bone Density, Bone Quality, and Hip Fracture

The effect of the degree of carboxylation of osteocalcin (OC) on the properties of bone is unclear. The aim of this study was to relate serum concentrations of total OC (tOC) and undercarboxylated OC (ucOC), measured with a two-site immunoassay, to bone mineral density (BMD) at the femoral neck and ultrasonic transmitted velocity (UTV) at the os calcis in 257 women aged 60–99 years, 22 of whom had sustained a hip fracture. There was an increase in tOC (r = 0.19, P= 0.003) and ucOC (r = 0.20, P= 0.002) with age. No significant difference in tOC or ucOC between subjects with and without hip fracture was found. Serum tOC was negatively correlated with femoral neck BMD (r =−0.23, P= 0.0001) and os calcis UTV (r =−0.29, P= 0.0001) and partial correlations indicated that these relationships were independent of age. Serum ucOC also correlated negatively with os calcis UTV (r =−0.21, P= 0.001) and less strongly with femoral neck BMD (r =−0.13, P= 0.052). After adjusting for age, only the relationship between ucOC and os calcis UTV remained significant (r =−0.16, P= 0.017). It is concluded that in women over 60 years, the increase in tOC reflects an age-related rise in bone remodeling, whereas the increase in ucOC reflects an age-related fall in vitamin K status. The stronger relationship of ucOC with UTV than BMD suggests that the rise in ucOC may perhaps relate more to changes in bone quality than mineral content. Higher serum ucOC concentrations in subjects with a history of hip fracture could not be confirmed. Received: 8 January 1997 / Accepted: 29 September 1997     

糖尿病大鼠骨代谢的变化

目的研究糖尿病早期骨代谢改变。方法测定６周实验性糖尿病（ＳＴＺ－ＤＭ）大鼠空腹血糖、ＨｂＡ１ｃ、胰岛素、钙离子浓度、骨钙素、降钙素、ＰＴＨ和维生素Ｄ３。收集２４ｈ尿，测定白蛋白、肌酐、吡啶酚。结果糖尿病大鼠与正常对照组相比，血清钙浓度显著升高［（１３５．８５±１１．２８）对（１１７．２１±６．５２）ｍｇ／Ｌ，Ｐ＜０．０１］，骨钙素水平升高［（０．０７±０．０４）对（０．０５±０．０１）ｎｇ／ｍｌ，Ｐ＜０．０５］，维生素Ｄ３水平显著降低［（７．６３±１．８８）对（１１．５５±４．１１）ｎｇ／ｍｌ，Ｐ＜０．０５］，尿吡啶酚／肌酐显著降低［（４．７９±０．７５）对（７５．８４±６０．６７）ｎｍｏｌ／ｍｍｏｌ，Ｐ＜０．０１］；而血清降钙素和甲状旁腺素水平改变无统计学意义。结论糖尿病状态下存在骨代谢异常，主要表现为维生素Ｄ３降低、骨钙素升高及尿吡啶酚水平降低。糖尿病性骨质疏松可能与维生素Ｄ３水平降低及由于胰岛素缺乏所致的骨胶原合成障碍有关     

Undercarboxylated osteocalcin and bone mass in 8–12 year old children with cystic fibrosis

Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation. METHODS: We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC). RESULTS: LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05); 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC). CONCLUSION: Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.     

Diurnal Variation in Total and Undercarboxylated Osteocalcin: Influence of Increased Dietary Phylloquinone

A diurnal variation exists in blood levels of the vitamin K-dependent bone protein osteocalcin. However, it is not known whether the carboxylated and undercarboxylated constituents of osteocalcin also vary. Therefore, osteocalcin and undercarboxylated osteocalcin were measured in specimens collected every 4 hours over a 24-hour period in nine healthy subjects (five males, four females) ages 20–33 years who were consuming a mixed diet containing 100 μg of phylloquinone. Osteocalcin and undercarboxylated osteocalcin were measured by radioimmunoassay (RIA) before and after treatment with barium sulfate. Although the percent undercarboxylated osteocalcin did not change, a diurnal variation was observed in total osteocalcin, carboxylated osteocalcin, and undercarboxylated osteocalcin, with peak concentrations at 4 a.m. and the lowest concentrations between 12 p.m. and 4 p.m. The difference between the total osteocalcin peak and trough concentrations averaged 28 ± 7 (SEM)%. There were no gender differences in these rhythms. The effect of dietary phylloquinone as a modulator of these rhythms was evaluated in a randomized study by increasing phylloquinone intake to 420 μg/day with fortified corn oil, split between the lunch and dinner meals. Total and carboxylated osteocalcin fluctuations and concentrations were not affected by the dietary treatment. The diurnal variation in undercarboxylated osteocalcin was abolished with supplementation and concentrations at 8 a.m. (14 hours following supplementation) (2.3 ± 0.2 ng/ml) were significantly lower than the unsupplemented levels (2.7 ± 0.2 ng/mL, P= 0.006). The percentage of undercarboxylated osteocalcin was similarly decreased after supplementation (19.7 ± 1.3%) in relation to the mixed diet cycle (24.2 ± 1.6%, P= 0.006) at 8 a.m. on the second day. Dietary supplementation induced a fluctuation in percentage undercarboxylated osteocalcin with a decline in levels starting at approximately 12 a.m. Therefore, additional dietary phylloquinone does not appear to modulate the total osteocalcin diurnal rhythm, but can influence its undercarboxylated component. Received: 14 June 1996 / Accepted: 22 August 1997