Regulation by adipocytokines of bone metabolism

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1)Role of adiponectin in differentiation of bone marrow stromal cellsWe examined effects of adiponectin on differentiation of mouse bone marrow stromal cell line ST2. Osteocalcin and PPARγ2 mRNA expressions were determined as osteoblastic and adipocytic differentiation markers, respectively. Cells were stained with Oil-Red O to demonstrate cellular accumulation of triglyceride. Treatment with adiponectin inhibited the expression of osteocalcin mRNA, wheras it had no effects on adipogenesis of ST2 cells. When we examined primary cultures of mouse bone marrow cells, we got essentially the same observations. Therefore, at least in mice, adiponectin seems to inhibit osteoblastic differentiation of bone marrow stromal cells and have no effects on their adipogenesis.2)Analyses of bone obtained from transgenic miceWe next investigated effects of adiponectin on bone in vivo. First, we could not any difference of bone histology in adiponectin-transgenic mice until 10 week of age. Second, heterozygous adiponectin knock-out mice showed no skeletal abnormality at birth. Homozygous knock-out mice were embryonic lethal and have not been investigated in detail in bone histology.3)Role of circulating leptin on bone in vivoRecent report suggests that effects of leptin on central nervous system suppress bone formation in mice through its activation of sympathetic nervous system. We examined effects of changes of circulating leptin levels on bone metabolism in some kinds of transgenic mice. Transgenic mice overexpressing leptin in liver had low bone mass, whereas those overexpressing soluble leptin receptor showed high bone mass. Circulating leptin levels had negative correlation with bone mass in these experimental mice. Thus, it is suggested that circulating leptin also has inhibitory effects on bone formation in vivo.