title: Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.
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.
authors.affiliation: Department of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shinoda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ogata
authors.forename: Toru
authors.initials: T
authors.lastname: Akune
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hoshi
authors.forename: Ung-il
authors.initials: UI
authors.lastname: Chung
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019898:Autocrine Communication; D001846:Bone Development / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism*; D002478:Cells, Cultured; D004703:Endocrine System / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics; D019899:Paracrine Communication; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D007328:Insulin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse