title: Gas7 mediates the differentiation of human bone marrow-derived mesenchymal stem cells into functional osteoblasts by enhancing Runx2-dependent gene expression.
abstract: The differentiation of bone marrow mesenchymal stem cells (MSCs) into osteoblasts is a crucial step during bone formation. However, the mechanisms regulating the early stages of osteogenic differentiation are not fully understood. In the present study, we found that growth-arrest specific gene 7b (Gas7b) was up-regulated during dexamethasone-induced differentiation of human MSCs (hMSCs) into osteoblasts. Knockdown of Gas7 using short-hairpin RNA decreased the expression of the osteogenic transcription factor Runx2 and its target genes alkaline phosphatase, type I collagen, osteocalcin (OC), and osteopontin. In addition, knockdown of Gas7 decreased matrix mineralization of dexamethasone-treated hMSCs in vitro. In contrast, ectopic expression of Gas7 isoforms a and b promoted gene expression associated with osteoblast differentiation and matrix mineralization, and also induced the mineralization of hMSCs in vitro. Furthermore, a gene reporter assay designed to monitor OC expression in hMSCs revealed that Runx2-dependent transcriptional activity was enhanced by over-expression of human Gas7 isoforms a and b. These findings reveal that Gas7 regulates the differentiation of hMSCs into osteoblasts by enhancing Runx2-dependent gene expression.
authors: Department of Biochemistry and Molecular Biology, Chang Gung University, Gueishan, Taoyuan 333, Taiwan, Republic of China.
authors: Feng-Chun
authors: FC
authors: Hung
authors: Yuhan
authors: Y
authors: Chang
authors: Sue
authors: S
authors: Lin-Chao
authors: Chuck C-K
authors: CC
authors: Chao
mesh_terms: D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D015533:Transcriptional Activation
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C114909:GAS7 protein, human; D009419:Nerve Tissue Proteins; C493709:RUNX2 protein, human; D015675:Osteocalcin