TY - JOUR
T1 - Bone morphogenetic protein-3b (BMP-3b) is expressed in adipocytes and inhibits adipogenesis as a unique complex
AU - Hino, J.
AU - Miyazawa, T.
AU - Miyazato, M.
AU - Kangawa, K.
N1 - Funding Information:
We thank Dr Shin-ichiro Nishimatsu for characterizing the antibody and CHO/BMP-3b CM and for helpful discussions. We thank Drs Yukari Date and Kazuki Sasaki for evaluating the antibody, and Dr Yuji Arai for the BMP-3b transgenic mice. We appreciate the technical assistance of Ms Michiyo Miyazaki. This study was supported in part by KAKENHI (20591107, 21790900, 21591189, 22126002), the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation of Japan and the Takeda Scientific Foundation.
PY - 2012/5
Y1 - 2012/5
N2 - Background: Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-Β (TGF-Β) superfamily. BMP-3b regulates osteogenesis and has critical roles in developing embryos. BMP-3b is expressed not only in the bone and developing embryos but also in adipose tissues. However, the functions of BMP-3b in adipose tissue are still unknown. Methods: BMP-3b expression was quantified in various adipose tissues and in the adipose-derived stromal-vascular fraction (SVF) and mature adipocyte fraction (AD.F) of mice. We also used 3T3-L1 preadipocytes to analyze the expression, function and molecular forms of BMP-3b. In order to determine the effects of BMP-3b on the adipogenesis of 3T3-L1 cells, BMP-3b siRNA-mediated knockdown and gene overexpression studies were performed, and a conditioned medium (CM) containing the BMP-3b protein was added to 3T3-L1 cell cultures. Adipocyte differentiation was evaluated by measuring the expression of adipogenic markers or by Oil Red O staining. The molecular form of BMP-3b that was secreted from the 3T3-L1 cells was analyzed by western blotting. Results: BMP-3b is expressed in all adipose tissues and is expressed at higher levels in preadipocytes than in mature adipocytes. In mesenteric adipose tissue, BMP-3b expression was increased in diet-induced obesity (DIO) mice as compared with that in control mice. BMP-3b was also expressed highly in 3T3-L1 cells. We showed that siRNA-mediated knockdown of endogenous BMP-3b expression in 3T3-L1 cells enhanced adipogenesis. Conversely, overexpressing BMP-3b inhibited adipocyte differentiation. We also showed that addition of CM containing the BMP-3b protein inhibited the differentiation of 3T3-L1 cells, and that this inhibitory effect was abolished by removing BMP-3b with an anti-BMP-3b antibody. Furthermore, BMP-3b was secreted from adipocytes as a unique non-covalent complex. Conclusion: These data suggest that BMP-3b is secreted from adipocytes and is involved in adipocyte differentiation.
AB - Background: Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-Β (TGF-Β) superfamily. BMP-3b regulates osteogenesis and has critical roles in developing embryos. BMP-3b is expressed not only in the bone and developing embryos but also in adipose tissues. However, the functions of BMP-3b in adipose tissue are still unknown. Methods: BMP-3b expression was quantified in various adipose tissues and in the adipose-derived stromal-vascular fraction (SVF) and mature adipocyte fraction (AD.F) of mice. We also used 3T3-L1 preadipocytes to analyze the expression, function and molecular forms of BMP-3b. In order to determine the effects of BMP-3b on the adipogenesis of 3T3-L1 cells, BMP-3b siRNA-mediated knockdown and gene overexpression studies were performed, and a conditioned medium (CM) containing the BMP-3b protein was added to 3T3-L1 cell cultures. Adipocyte differentiation was evaluated by measuring the expression of adipogenic markers or by Oil Red O staining. The molecular form of BMP-3b that was secreted from the 3T3-L1 cells was analyzed by western blotting. Results: BMP-3b is expressed in all adipose tissues and is expressed at higher levels in preadipocytes than in mature adipocytes. In mesenteric adipose tissue, BMP-3b expression was increased in diet-induced obesity (DIO) mice as compared with that in control mice. BMP-3b was also expressed highly in 3T3-L1 cells. We showed that siRNA-mediated knockdown of endogenous BMP-3b expression in 3T3-L1 cells enhanced adipogenesis. Conversely, overexpressing BMP-3b inhibited adipocyte differentiation. We also showed that addition of CM containing the BMP-3b protein inhibited the differentiation of 3T3-L1 cells, and that this inhibitory effect was abolished by removing BMP-3b with an anti-BMP-3b antibody. Furthermore, BMP-3b was secreted from adipocytes as a unique non-covalent complex. Conclusion: These data suggest that BMP-3b is secreted from adipocytes and is involved in adipocyte differentiation.
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U2 - 10.1038/ijo.2011.124
DO - 10.1038/ijo.2011.124
M3 - Article
C2 - 21712809
AN - SCOPUS:84860729957
SN - 0307-0565
VL - 36
SP - 725
EP - 734
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 5
ER -
