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Gas7 mediates the differentiation of human bone marrow‐derived mesenchymal stem cells into functional osteoblasts by enhancing Runx2‐dependent gene expression
Author(s) -
Hung FengChun,
Chang Yuhan,
LinChao Sue,
Chao Chuck C.K.
Publication year - 2011
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21425
Subject(s) - runx2 , gene knockdown , osteopontin , mesenchymal stem cell , osteoblast , osteocalcin , cellular differentiation , chemistry , microbiology and biotechnology , ectopic expression , gene expression , small hairpin rna , alkaline phosphatase , biology , endocrinology , in vitro , gene , biochemistry , enzyme
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. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1528–1535, 2011