title: Role of Osteoprotegerin (OPG) in Bone Marrow Adipogenesis.
abstract: OBJECTIVE
  Bone marrow adipogenesis is one of the major characteristics of aged bone. Bone marrow mesenchymal stem cells (BMMSCs) prefer to differentiate into adipocytes instead of osteoblasts in the bone marrow cavity in aged hosts. The mechanism of formation and function of adipocytes in aged bone marrow needs further investigation. Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor (TNFR) super family, and it can inhibit the activities of osteoclasts. We found that adipocyte numbers increased in the bone marrow of Opg knockout mice. In this study, we investigated the role of OPG in the differentiation of BMMSCs and bone marrow adipogenesis.
  
  
  METHODS
  Histological analyses were performed on the bone tissues of Opg knockout (Opg-KO) and wild-type (WT) mice of different ages. BMMSCs obtained from mice were cultured in vitro to evaluate their differentiation abilities.
  
  
  RESULTS
  With aging, the expression of Opg in the bone marrow of WT mice markedly decreased, but that of the adipogenic specific transcription factor peroxisome proliferator-activated receptor γ (Ppar-γ) increased. Adipocytes formed in the bone marrow of Opg-KO mice at a relative young age, and the number of adipocytes increased dramatically with age. Compared with the WT control, the osteogenic differentiation of Opg-KO BMMSCs decreased, but the adipogenic differentiation increased. Moreover, exogenous OPG could inhibit the adipogenic differentiation and promote the osteogenic differentiation of Opg-KO BMMSCs in vitro.
  
  
  CONCLUSIONS
  OPG plays an important role in regulating BMMSC differentiation and bone marrow adipogenesis.
authors.affiliation: Department of Implantology, School and hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Jing
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin