BMP14 induces tenogenic differentiation of bone marrow mesenchymal stem cells in vitro

摘要

Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells, which have the capacity to differentiate into various types of mesenchymal cell phenotypes, including osteoblasts, chondroblasts, myoblasts and tendon fibroblasts (TFs). The molecular mechanism for tenogenic differentiation of BMSCs is still unknown. The present study investigated the effects of bone morphogenetic protein (BMP) 14 on BMSC differentiation in vitro. It was revealed that BMP14 significantly increased the expression of tendon markers (scleraxis and tenomodulin) at the mRNA and protein level, which led to the upregulation of sirtuin 1 (Sirt1) expression. The gain or loss of Sirt1 function may promote or inhibit tenogenic differentiation by deacetylating the peroxisome proliferator-activated receptor (PPAR)-gamma. BMP14 also triggered the phosphorylation of c-Jun N-terminal kinase (JNK) and Smad1; overexpression of Sirt1 significantly increased the phosphorylation and knockdown of Sirt1 significantly decreased the phosphorylation. The inhibition of JNK and Smad significantly increased the acetylation of PPAR gamma and inhibited the expression of tenogenic differentiation markers. These results suggest that BMP14 may induce the tenogenic differentiation of BMSCs via the Sirt1-JNK/Smad1-PPAR gamma signaling pathway. The present study provided a cellular and molecular basis for the development of novel therapeutic strategies for tendon healing.