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Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways

2006; Wiley; Volume: 99; Issue: 1 Linguagem: Inglês

10.1002/jcb.20890

1097-4644

Yusuke Shinoda, Masayuki Yamaguchi, Naoshi Ogata, Toru Akune, Naoto Kubota, Toshimasa Yamauchi, Yasuo Terauchi, Takashi Kadowaki, Yasuhiro Takeuchi, Seiji Fukumoto, Toshiyuki Ikeda, Kazuto Hoshi, Ung‐il Chung, Kozo Nakamura, Hiroshi Kawaguchi,

Vitamin D Research Studies

Abstract Since interaction between bone and lipid metabolism has been suggested, this study investigated the regulation of bone metabolism by adiponectin, a representative adipokine, by analyzing deficient and overexpressing transgenic mice. We initially confirmed that adiponectin and its receptors were expressed in osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone not only through an endocrine pathway as a hormone secreted from fat tissue, but also through an autocrine/paracrine pathway. There was no abnormality in bone mass or turnover of adiponectin‐deficient (Ad−/−) mice, possibly due to an equivalent balance of the two pathways. In the culture of bone marrow cells from the Ad−/− mice, osteogenesis was decreased compared to the wild‐type (WT) cell culture, indicating a positive effect of endogenous adiponectin through the autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we analyzed transgenic mice overexpressing adiponectin in the liver, and found no abnormality in the bone. Addition of recombinant adiponectin in cultured osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action of circulating adiponectin was negative for bone formation. In the presence of insulin, however, this suppression was blunted, and adiponectin enhanced the insulin‐induced phosphorylations of the main downstream molecule insulin receptor substrate‐1 and Akt. These lines of results suggest three distinct adiponectin actions on bone formation: a positive action through the autocrine/paracrine pathway by locally produced adiponectin, a negative action through the direct pathway by circulating adiponectin, and a positive action through the indirect pathway by circulating adiponectin via enhancement of the insulin signaling. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.