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 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.
Akune
Toru
T
Department of Orthopaedic Surgery, University of Tokyo, Japan.
Ohba
Shinsuke
S
Kamekura
Satoru
S
Yamaguchi
Masayuki
M
Chung
Ung-Il
UI
Kubota
Naoto
N
Terauchi
Yasuo
Y
Harada
Yoshifumi
Y
Azuma
Yoshiaki
Y
Nakamura
Kozo
K
Kadowaki
Takashi
T
Kawaguchi
Hiroshi
H
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D018390:Gene Targeting; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D010052:Ovariectomy; D010053:Ovary / Q000378:metabolism / Q000601:surgery; D011859:Radiography; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D013977:Tibia / Q000000981:diagnostic imaging; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors