title: Deficiency of adiponectin protects against ovariectomy-induced osteoporosis in mice.
abstract: Adipokine adiponectin (APN) has been recently reported to play a role in regulating bone mineral density (BMD). To explore the mechanism by which APN affects BMD, we investigated BMD and biomechanical strength properties of the femur and vertebra in sham-operated (Sham) and ovariectomized (OVX) APN knockout (KO) mice as compared to their operated wild-type (WT) littermates. The results show that APN deficiency has no effect on BMD but induces increased ALP activity and osteoclast cell number. While OVX indeed leads to significant bone loss in both femora and vertebras of WT mice with comparable osteogenic activity and a significant increase in osteoclast cell number when compared to that of sham control. However, no differences in BMD, ALP activity and osteoclast cell number were found between Sham and OVX mice deficient for APN. Further studies using bone marrow derived mesenchymal stem cells (MSCs) demonstrate an enhanced osteogenic differentiation and extracellular matrix calcification in APN KO mice. The possible mechanism for APN deletion induced acceleration of osteogenesis could involve increased proliferation of MSCs and higher expression of Runx2 and Osterix genes. These findings indicate that APN deficiency can protect against OVX-induced osteoporosis in mice, suggesting a potential role of APN in regulating the balance of bone formation and bone resorption, especially in the development of post-menopausal osteoporosis.
authors.affiliation: Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Pei-xia
authors.initials: PX
authors.lastname: Wang
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Wu
authors.forename: Su-ying
authors.initials: SY
authors.lastname: Dang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying-yin
authors.initials: YY
authors.lastname: Ni
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Gao
authors.forename: Shun-yuan
authors.initials: SY
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.forename: Zhu-gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Xiao-fen
authors.initials: XF
authors.lastname: Pang
mesh_terms: D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000172:deficiency* / Q000235:genetics; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D010052:Ovariectomy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D000469:Alkaline Phosphatase; D002118:Calcium