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Background: Cytokines including transforming growth factor beta 1 (TGF-β1) and osteoprotegerin (OPG) are closely related to bone metabolism. However, the relationships between TGF-β1, OPG and risk of osteoporosis in native Chinese women are unknown. Our research indicated that there is a positive correlation between TGF-β1 and bone mineral density (BMD) T-score, and a negative correlation between OPG and T-score. The risk of osteoporosis is reduced as TGF-β1 increases and increases as OPG was raised. We investigated correlations of BMD T-scores with circulating TGF-β1 and BMD T-scores with circulating OPG in healthy native Chinese women, and to study the effects of changes in TGF-β1 and OPG on osteoporosis., Methods: This was a cross-sectional study of 691 healthy native Chinese women aged 20-80 years. Concentrations of serum TGF-β1 and OPG were determined. BMD T-scores at the posteroanterior spine, left hip, and forearm were measured by dual-energy X-ray absorptiometry., Results: There were positive correlations between serum TGF-β1 and T-scores at the various skeletal sites (r=0.167-0.285, all P=0.000) and negative correlations between serum OPG and T-scores (r=-0.179 to -0.270, all P=0.007-0.000). After adjusting for age and BMI, correlations between TGF-β1 and T-score at the lumbar vertebrae and ultradistal forearm, and between OPG and T-score at the ultradistal forearm in premenopausal subjects, remained statistically significant. Multivariate linear stepwise analysis showed that TGF-β1 could explain 1.9-8.3% of T-score variation at each skeletal site. OPG could explain 2.4-4.4% of T-score variation. When TGF-β1 and OPG concentrations were grouped according to quartile intervals, T-score and the prevalence and risk of osteoporosis varied with changes in the cytokines., Conclusions: The risk of osteoporosis in native Chinese women increased as circulating TGF-β1 was reduced and OPG was raised., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Adiponectin may exert a negative effect on bone metabolism by regulating osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) expression. However, the action of adiponectin on bone may be influenced by estrogen in women. The present study was undertaken to investigate the effects of 17β-estradiol (E2) on adiponectin-regulated OPG and RANKL expression in human osteoblast. Human osteoblasts were treated with α-MEM containing 10μg/ml adiponectin alone or together with 10(-10) to 10(-8)M E2 for 12-48h. Cells were also treated with α-MEM containing 10μg/ml adiponectin together with 10(-8)M E2 plus p38 agonist-anisomycin or estrogen receptor (ER) antagonist ICI182780 for 48h. The effects of E2 were also investigated by knockdown of ERs or overexpression of p38 MAPK in osteoblasts. Further, we examined the effects of E2 on adiponectin-dependent osteoclastogenesis by the co-culture systems of osteoblast and CD14+ peripheral blood monocytes (PBMCs). Real-time quantitative PCR (RT-PCR) and ELISA were used to detect OPG/RANKL mRNA and their corresponding protein expression, Western Blot was used to analyze the phosphorylated p38 (p-p38) levels. The results showed that E2 blocked adiponectin-induced p38 phosphorylation, decreased adiponectin-regulated OPG/RANKL mRNA and protein expression in a dose- and time-dependent manner. ICI182780 or knockdown of ERs abolished the effects of E2 on adiponectin-dependent p38 phosphorylation and OPG/RANKL expression. Furthermore, anisomycin or overexpression of p38 also reserved the effects of E2 on adiponectin-dependent p38 phosphorylation and OPG/RANKL expression. E2 inhibited adiponectin-dependent osteoclastogenesis in the co-culture systems of osteoblast and CD14+ PBMCs, whereas anisomycin, ICI182780, knockdown of ERs and overexpression of p38 significantly reversed this response. In conclusions, our findings demonstrated, through blocking the activation of adiponectin-induced p38 MAPK, E2 suppressed the adiponectin-regulated OPG/RANKL expression and then inhibited osteoclastogenesis, which suggested that estrogen would suppress the effect of adiponectin on bone metabolism., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: Omentin-1 (also known as intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is inversely related to obesity. Our previous study showed that omentin-1 inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs) in vitro. This study was undertaken to investigate the effects of omentin-1 on arterial calcification and bone metabolism in vivo., Methods and Results: In vitro, omentin-1 stimulated production of osteoprotegerin (OPG) and inhibited production of receptor activator for nuclear factor κB ligand (RANKL) in both CVSMCs and osteoblasts. In vivo, adenovirus-mediated over-expression of omentin-1 attenuated arterial calcification and bone loss in OPG(-/-) mice. All these in vitro and in vivo actions were abrogated by blockade of the PI3K-Akt signalling pathway. Furthermore, omentin-1 reduced serum levels of RANKL, tartarate-resistant acid phosphatase-5b and osteocalcin, all of which are increased dramatically in OPG(-/-) mice., Conclusion: These data suggest that omentin-1 ameliorates arterial calcification and bone loss in vivo through the regulation of the RANK signalling pathway.

Background: The relationship between the levels of gonadotropic hormones and bone metabolism-related cytokines in Chinese women is unclear. We investigated the relationship between FSH and LH and OPG, leptin, TGF-beta1, and TGF-beta2 in Chinese women., Methods: A cross-sectional study of 694 Chinese women, aged 20 to 82y was conducted. Levels of serum FSH, LH, OPG, leptin, TGF-beta1, and TGF-beta2 were determined., Results: In premenopausal females, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels seemly showed no correlation with the cytokine levels. In perimenopausal females, serum FSH and LH levels showed significant positive correlation with osteoprotegerin (OPG) and transforming growth factor-beta2 (TGF-beta2) levels (r=0.286 to 0.405, all P=0.000), whereas they showed negative correlation with TGF-beta1 levels (r=-0.413 and -0.354, all P=0.000). In postmenopausal females, FSH and LH levels showed positive correlation with OPG levels (r=0.247 and 0.241, all P=0.000), negative correlation with leptin and TGF-beta1 levels (r=-0.234 to -0.319, all P=0.000), and no correlation with TGF-beta2 levels. Multiple linear regression stepwise analysis revealed the following results. In premenopausal females, 2.0% and 1.5% of the changes in LH could be explained by OPG and leptin, respectively, while 1.9% of the changes in OPG could be explained by LH. In perimenopausal females, the determinants of OPG and TGF-beta1 on FSH were 10.9% and 17.0%, respectively, and the determinants of OPG, TGF-beta1 and TGF-beta2 on LH were 4.5%, 4.9% and 16.4%, respectively. The determinants of FSH and LH on OPG were 14.5% and 2.5%, respectively. The determinant of FSH on TGF-beta1 was 4.5%, while the determinant of LH on TGF-beta2 was 16.4%. In postmenopausal females, the determinants of leptin and OPG on FSH were 10.2% and 2.8%, respectively, and the determinants of OPG and TGF-beta1 on LH were 5.8% and 2.3%, respectively. The determinant of FSH on OPG, leptin and TGF-beta1 were 6.1%, 3.4% and 9.2%., Conclusions: These results indicate that age-related gonadotropic hormone levels are associated with changes in OPG, TGF-beta1, TGF-beta2 and leptin, and change with menopausal status., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Transforming growth factor-beta 1 (TGF-beta1), TGF-beta2, osteoprotegerin (OPG), and leptin are important cytokines in the regulation of bone remodeling. We investigated the relationship of TGF-beta1 and TGF-beta2 concentrations with those of OPG and leptin in Chinese females., Methods: The serum concentrations of TGF-beta1, TGF-beta2, OPG, and leptin were measured by ELISA in 459 healthy Chinese females aged 25-80 y., Results: The mean values (+/-SD) of the serum concentrations of TGF-beta1, TGF-beta2, OPG, and leptin in Chinese females were 29.7+/-1.69 microg/l, 13.7+/-3.86 microg/l, 3.81+/-1.96 pmol/l, and 10.5+/-2.01 microg/l, respectively. Further, the serum TGF-beta1 concentrations of postmenopausal women were significantly lower than those of perimenopausal and premenopausal women (24.3+/-1.59 vs 33.4+/-1.69 and 37.6+/-1.64, respectively), while the TGF-beta2 concentrations of postmenopausal women were significantly higher than those of perimenopausal and premenopausal women (14.6+/-3.91 vs 13.5+/-3.93 and 11.7+/-2.68, respectively). The serum TGF-beta1 concentration was found to be significantly negatively correlated with age (r=-0.335, P=0.000) and the TGF-beta2 concentration, to be significantly positively correlated with age (r=0.230, P=0.000). The TGF-beta1 concentration was found to be significantly negatively correlated with both TGF-beta2 (r=-0.261, P=0.000) and OPG (r=-0.313, P=0.000) concentrations; a significantly positive correlation was found between the TGF-beta1 and leptin concentrations (r=0.164, P=0.000) and between TGF-beta2 and OPG concentrations (r=0.432, P=0.000)., Conclusion: These results provide age-related reference values of TGF-beta1 and TGF-beta2 in Chinese adult women, and reveal the relationships between these cytokines.

Objective: To investigate the possible mechanism by which adiponectin influences the osteoclastogenesis., Methods: Human osteoblasts were cultured in vitro and adiponectin of the concentrations 0, 3, 10, and 30 microg/ml were added for 48 hours to investigate the dose-dependent effect on the mRNA and protein expression of osteoprotegerin (OPG) in osteoblasts, and adiponectin of the concentrations 0 or 30 microg/ml was added for 0-48 hours to investigate the time-dependent effect. Fluorescent quantitation PCR and ELISA were used to detect the expression of OPG and receptor activator of nuclear factor-kappaB ligand (RANKL). Other human osteoblasts were cultured with CD14 + peripheral blood mononuclear cells (PBMCs), and incubated together with adiponectin of the concentration of 30 microg/ml for 14 days, and then stained by antitartaric acid phosphatase, a marker enzyme of osteoclast., Results: The expression levels of mRNA and protein of OPG in osteoblasts were 100% +/- 9%, 68% +/- 7%, 47% +/- 8%, and 30% +/- 5%, and (9.2 +/- 0.3), (6.6 +/- 0.4), (4.1 +/- 0.4), and (2.6 +/- 0.4) ng/ml respectively after incubation with adiponectin of the concentrations of 0, 3, 10, and 30 microg/ml for 48 hours. The mRNA and protein expression levels of RANKL were 100% +/- 5%, 165% +/- 8%, 213% +/- 6%, and 316% +/- 10%, and (1.3 +/- 0.2), (2.1 +/- 0.1), (2.3 +/- 0.2), and (2.8 +/- 0.1) ng/ml respectively. Adiponectin inhibited the osteoblast OPG expression and promoted the osteoblast RANKL expression dose- and time-dependently (P < 0.05). Adiponectin induced the osteoclast formation in the coculture systems of osteoblast and PBMCs systems., Conclusion: Adiponectin increases osteoclast formation via stimulating RANKL and inhibiting OPG production in the osteoblasts, which may be one of the mechanisms adiponectin influences the osteoclastogenesis thereby.

Background: Osteoprotegerin (OPG) and leptin are important cellular factors in the regulation of bone remodeling. We investigated the serum OPG and leptin in Chinese women., Methods: The serum OPG and leptin in 690 Chinese women aged 20-81 y were measured by an ELISA. The values of OPG and leptin in women of other races were acquired from previous reports on the same., Results: The geometric mean values (+/- SD) of the serum OPG and leptin in Chinese women were 3.42+/-1.91 pmol/l and 10.5+/-1.99 microg/l, respectively. Further, the serum OPG (4.39+/-1.85 vs 2.74+/-1.81) and leptin (11.4+/-2.21 vs 9.68+/-1.81) in postmenopausal women were significantly higher than in premenopausal women. The serum OPG in middle-aged Chinese women was significantly higher than that in middle-aged Austrian and Icelandic women; however, this is quite contrary to the results obtained in the case of old-aged women. The values of serum leptin in Chinese women were significantly lower than those in white, black, and Mexican American women., Conclusions: These results provide reliable reference values for OPG and leptin in Chinese adult women. The serum of OPG and leptin differ with ethnicity.

Unlabelled: Our study indicates that recombinant adiponectin induced RANKL and inhibited OPG expression in human osteoblasts through the AdipoR1/p38 MAPK pathway, and these responses contributed to the adiponectin-induced osteoclasts formation in the co-culture of osteoblast and peripheral blood monocytes systems. These findings showed that adiponectin increased osteoclast formation indirectly through stimulating RANKL and inhibiting OPG production in osteoblasts. It also suggests the pharmacological nature of recombinant adiponectin that indirectly induces osteoclasts formation., Introduction: Recently, adiponectin has emerged as an element in the regulation of bone metabolism, but the mechanism remains. This study was undertaken to investigate the action of adiponectin on osteoclastogenesis through revealing RANKL and osteoprotegerin (OPG) expression in osteoblasts and osteoclast formation., Materials and Methods: Real-time quantitative PCR and ELISA were used to detect RANKL and OPG mRNA and protein expression in cultured human osteoblasts. The involved signal pathway was studied using mitogen-activated protein kinase (MAPK) inhibitor and adiponectin receptor 1 (AdipoR1) siRNA. The effects of recombinant adiponectin on osteoclasts formation also were examined in the co-culture systems of osteoblast and peripheral blood monocytes (PBMCs) systems or purified CD14 + PBMCs cultures., Results: Our study showed that recombinant adiponectin induced RANKL and inhibited OPG mRNA expression in human osteoblasts in a dose- and time-dependent manner. Adiponectin also increased soluble RANKL and decreased OPG secretion in osteoblasts conditioned media. Suppression of AdipoR1 with siRNA abolished the adiponectin-regulated RANKL and OPG mRNA expression in osteoblasts. Furthermore, pretreatment of osteoblasts with the MAPK inhibitor SB203580 abolished adiponectin-regulated RANKL and OPG mRNA expression. Adiponectin induced osteoclast formation in the co-culture systems of osteoblast and PBMCs systems, and OPG entirely blocked this response. However, adiponectin had no direct effect on the differentiation of osteoclast precursor purified CD14 + PBMCs., Conclusions: These data indicate that recombinant adiponectin induced RANKL and inhibited OPG expression in human osteoblasts through the AdipoR1/p38 MAPK pathway, and these responses contributed to the adiponectin-induced osteoclast formation in the co-culture of osteoblast and PBMCs systems. These findings showed that adiponectin increased osteoclast formation indirectly through stimulating RANKL and inhibiting OPG production in osteoblasts. It suggests the pharmacological nature of recombinant adiponectin that indirectly induces osteoclasts formation.