RRC ID |
42611
|
著者 |
Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, Terauchi Y, Kadowaki T, Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K, Chung UI, Nakamura K, Kawaguchi H.
|
タイトル |
Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.
|
ジャーナル |
J Cell Biochem
|
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.
|
巻・号 |
99(1)
|
ページ |
196-208
|
公開日 |
2006-9-1
|
DOI |
10.1002/jcb.20890
|
PMID |
16598753
|
MeSH |
Adiponectin / genetics
Adiponectin / metabolism*
Animals
Autocrine Communication*
Bone Development / genetics
Bone Marrow Cells / cytology
Bone Marrow Cells / physiology
Bone and Bones / metabolism*
Cells, Cultured
Endocrine System / metabolism*
Insulin / metabolism
Liver / physiology
Male
Mice
Mice, Transgenic
Osteoclasts / cytology
Osteoclasts / physiology
Osteogenesis / genetics
Paracrine Communication*
Receptors, Adiponectin
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Signal Transduction
|
IF |
4.237
|
引用数 |
201
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
ST2(RCB0224) |