PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors
PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors
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DOI：
10.1172/jci200419900
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发表时间：
2004-03-01
影响因子：
15.9
通讯作者：
Kawaguchi, H
中科院分区：
文献类型：
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作者：
Akune, T;Ohba, S;Kawaguchi, H
基于衰老与骨髓成骨减少和脂肪生成增加的相互关系，以及成骨细胞和脂肪细胞具有共同的祖细胞，本研究探讨了脂肪细胞分化的关键调节因子PPARgamma在骨代谢中的作用。纯合子ppargamγ缺陷胚胎干细胞不能分化为脂肪细胞，但能自发分化为成骨细胞，并通过重新引入PPARgammagene恢复成骨细胞。杂合子ppargamma缺陷小鼠表现出高骨量，成骨细胞生成增加，但成骨细胞和破骨细胞功能正常，这种影响不是由胰岛素或瘦素介导的。PPARgamma单倍体功能不全的成骨作用随着年龄的增长而变得突出，但在卵巢切除术后没有改变。在骨髓细胞培养中，pparty单倍体不足被证实能促进成骨细胞的形成，但不影响分化成骨细胞或破骨细胞谱系细胞的培养。本研究证明了体内骨代谢的PPARgamma依赖性调节，因为PPARgamma不足通过刺激骨髓祖细胞的成骨细胞发生而增加骨量。
Based on the fact that aging is associated with a reciprocal decrease of osteogenesis and an increase of adipogenesis in bone marrow and that osteoblasts and adipocytes share a common progenitor, this study investigated the role of PPARgamma, a key regulator of adipocyte differentiation, in bone metabolism. Homozygous PPARgamma-deficient ES cells failed to differentiate into adipocytes, but spontaneously differentiated into osteoblasts, and these were restored by reintroduction of the PPARgammagene. Heterozygous PPARgamma-deficient mice exhibited high bone mass with increased osteoblastogenesis, but normal osteoblast and osteoclast functions, and this effect was not mediated by insulin or leptin. The osteogenic effect of PPARgamma haplo-insufficiency became prominent with aging but was not changed upon ovariectomy. The PPARy haplo-insufficiency was confirmed to enhance osteoblastogenesis in the bone marrow cell culture but did not affect the cultures of differentiated osteoblasts or osteoclast-lineage cells. This study demonstrates a PPARgamma-dependent regulation of bone metabolism in vivo, in that PPARgamma insufficiency increases bone mass by stimulating osteoblastogenesis from bone marrow progenitors.