title: Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma.
abstract: Growth and differentiation factor 11 (GDF11) is a TGF-β family member that is expressed widely and plays multiple roles, including regulating axial skeletal patterning during development. However, the function of GDF11 in the bone is barely understood. Here we identify GDF11 as a potent regulator of bone homeostasis. GDF11 level is significantly decreased in the plasma and bone marrow of aging mice and mice with osteoporosis. Pharmacologic GDF11 gain of function leads to a striking increase in osteoblastogenesis and inhibits adipogenesis from bone marrow mesenchymal stem cells by altering the gene expression pattern. GDF11 inhibits the activity of the peroxisome proliferator-activated receptor γ (PPAR-γ) by promoting its SUMOylation. Therefore, GDF11 is a critical rheostat for bone turnover and a key integrator of bone homeostasis. These results reveal that skeletal fragility may be reduced by chronic GDF11 administration.
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China. Electronic address: tieyiyang1962@sohu.com.
authors.forename: Tieyi
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Xinbing
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Ye
mesh_terms: D050156:Adipogenesis; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D055412:Growth Differentiation Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology*; D010024:Osteoporosis / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; D047495:PPAR gamma
keywords: GDF11; Osteoblastogenesis; Osteoporosis; PPAR-γ