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.