I. Kanazawa Pages 5481 - 5492 ( 12 )
Adiponectin has attracted widespread attention because of its pivotal role in glucose metabolism and energy homeostasis. Adiponectin and its receptor are shown to be expressed in osteoblasts, suggesting that adiponectin might affect bone metabolism. A number of clinical studies have shown that serum adiponectin is negatively associated with bone mineral density (BMD) and positively with biochemical markers of bone turnover, suggesting that adiponectin may be a negative regulator of bone mass. However, most in vitro studies demonstrate that adiponectin stimulates the differentiation and mineralization of osteoblasts as well as the expression of osteocalcin. Adiponectin indirectly stimulates osteoclast differentiation via receptor activator for nuclear factor B ligand and osteoprotegerin expression in osteoblasts, while adiponectin directly inhibits osteoclast activity and bone resorption. These in vitro findings suggest that adiponectin stimulates bone formation and remodeling as well as inhibits bone resorption. In contrast, previous in vivo studies using overexpression and knockout mice of adiponectin have produced controversial results. On the other hand, recent studies have shown that osteocalcin derived form osteoblasts acts as a hormone regulating glucose metabolism and fat mass. Osteocalcin could decrease fat pads and stimulate the expression of adiponectin in adipocytes, suggesting that bone metabolism is associated with fat metabolism through adiponectin and osteocalcin. In this review, I summarize the effect of adiponectin on osteoblasts and osteoclasts in vitro and in vivo, the association of adiponectin with BMD and bone markers in humans, and the role of adiponectin in the endocrine loop between bone and fat metabolism.
Adiponectin, osteoblast, osteoclast, bone mineral density, bone turnover, fracture risk, osteocalcin, type 2 diabetes mellitus, "adipocytes", suppresses tumour
Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan.