title: GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells.
abstract: Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β superfamily. Recent studies confirmed that GDF11 plays an important role in regulating the regeneration of brain, skeletal muscle, and heart during aging; however, its role in bone metabolism remains unclear. Thus, the aim of this study was to determine the effects of GDF11 on bone metabolism, including bone formation and bone resorption, both in vitro and in vivo. Our results showed that GDF11 inhibited osteoblastic differentiation of bone marrow mesenchymal stem cells in vitro. Mechanistically, GDF11 repressed Runx2 expression by inducing SMAD2/3 phosphorylation during osteoblast differentiation. Moreover, intraperitoneal injection of GDF11 inhibited bone formation and accelerated age-related bone loss in mice. Our results also showed that GDF11 had no effect on osteoclast differentiation or bone resorption both in vitro and in vivo. These results provide a further rationale for the therapeutic targeting of GDF11 for the treatment of age-related osteoporosis.
authors.affiliation: Department of Metabolism & Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Metabolism & Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|Department of Orthopaedics Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Tu
authors.affiliation: Department of Metabolism & Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: Department of Metabolism & Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.|National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, The Xiangya Hospital of Central South University, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Tie-Jian
authors.initials: TJ
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Tang
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Metabolism & Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China. xianghangluo@sina.com.|National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China. xianghangluo@sina.com.
authors.forename: Xiang-Hang
authors.identifier: 0000-0001-6413-572X
authors.initials: XH
authors.lastname: Luo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D055412:Growth Differentiation Factors / Q000378:metabolism* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors; D051899:Smad2 Protein; D051900:Smad3 Protein
keywords: Aging; Bone marrow mesenchymal stem cells; Growth differentiation factor 11; Osteoblast; Osteoporosis