PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors

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 met...

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Bibliographic Details
Published in:The Journal of clinical investigation 2004-03, Vol.113 (6), p.846-855
Main Authors: Akune, Toru, Ohba, Shinsuke, Kamekura, Satoru, Yamaguchi, Masayuki, Chung, Ung-Il, Kubota, Naoto, Terauchi, Yasuo, Harada, Yoshifumi, Azuma, Yoshiaki, Nakamura, Kozo, Kadowaki, Takashi, Kawaguchi, Hiroshi
Format: Article
Language:English
Subjects:
Animals
Bone and Bones - metabolism
Bone Marrow Cells - metabolism
Female
Femur - diagnostic imaging
Gene Targeting
Mice
Osteoblasts - metabolism
Osteogenesis - physiology
Ovariectomy
Ovary - metabolism
Ovary - surgery
Radiography
Receptors, Cytoplasmic and Nuclear - deficiency
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Stem Cells - metabolism
Tibia - diagnostic imaging
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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 PPARgamma gene. 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 haploinsufficiency became prominent with aging but was not changed upon ovariectomy. The PPARgamma haploinsufficiency 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.
ISSN:0021-9738