Relationships between age-related biochemical markers of bone turnover and OPG, TGF-ß1 and TGF-ß2 in native Chinese women.

Osteoprotegerin (OPG), transforming growth factor-ß1 (TGF-ß1) and TGF-ß2 are cytokines closely associated with bone metabolism. However, their association with bone turnover markers in native Chinese women remains unknown. The study aims to investigate the relationship between bone metabolism related cytokines including OPG, TGF-ß1, TGF-ß2 and bone turnover markers in native Chinese women. The cross-sectional study was conducted on 691 healthy Chinese women (20-80 years old). Levels of OPG, TGF-ß1, TGF-ß2, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. The present study showed that OPG and TGF-ß2 had positive correlation with BAP, OC, uNTX, uCTX and uDPD, while TGF-ß1 showed negative correlation with BAP, OC, sCTX, uNTX and uCTX, and most of the coefficients of partial correlation remained significant after adjustments for age and body mass index (BMI). Multiple linear regression stepwise analysis showed that OPG and TGF-ß2 were positive determinative factors for BAP, sCTX, uNTX and uCTX, which could explain 0.6-16.6% of the variation in these markers. TGF-ß1 was a negative determinative factor for BAP, OC, sCTX and uCTX, which could explain 0.7-7.3% of the variation in these markers. This study suggested that measuring bone turnover indicators and serum cytokines simultaneously might help evaluating changes in bone turnover rate caused by aging or menopause in women.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.