Role of bone marrow adipogenesis for bone formation and its abnormality in senile osteoporosis

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1) Role of interteukin-11(IL-11) in adipogenesis and osteoblastogenesis in bone marrow.We have previously shown that decreased IL-11 expression is tightly associated with impaired bone formation in senile osteoporosis model SAM-P6 mice. To further investigate how IL-11 is involved in bone metabolism, we examined effects of IL-11 on differentiation of both adipocytes and osteoblasts in bone marrow. Our results indicate that IL-11 inhibits transcriptional activity of PPARγ, essential for adipocyte differentiation, and stimulates that of Smad1, indispensable for osteoblastic differentiation2) In vivo effects of IL-11 on bone metabolismWe next investigated effects of IL-11 on bone metabolism in vivo using tansgenic mice overexpressing human IL-11 gene. Bone formation was stimulated but bone resorption was not changed in IL-11 transgenic mice, resulting in thicker and stronger cortical bone than control littermates. More importantly, cortical bone loss was not observed in IL-11 transgenic mice with aging. These results suggest that IL-11 stimulates bone formation and prevents bone loss with aging.3) Involvement of PPARγ in osteoblastogenesis and adipngenflsis in bone marrowWe examined if PPARγ was involved in osteoblastogenesis as well as adipogenesis in bone marrow stromal cells, using mouse bone marrow stromal cell line ST2 stably expressing dominant negative PPARγ (DN-ST2). DN-ST2 cells were confirmed not to be differentiated into adipocytes. These cells were also not differentiated into osteoblasts in vitro, suggesing that PPARγ actions are required for osteobliastogenesis.