MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis

Abstract

MicroRNAs (miRNAs) have recently been recognized to have a role in human orthopedic disorders. The objective of our study was to explore the expression profile and biological function of miRNA-17-5p (miR-17-5p), which is well known to be related to cancer cell proliferation and invasion, in osteoblastic differentiation and in cell proliferation. The expression levels of miR-17-5p in the femoral head mesenchymal stem cells of 20 patients with non-traumatic osteonecrosis (ON) and 10 patients with osteoarthritis (OA) were examined by quantitative reverse transcription-PCR (qRT–PCR). Furthermore, the interaction between miR-17-5p and SMAD7 was observed. We found that in non-traumatic ON samples the level of mature miR-17-5p was significantly lower than that of OA samples (P=0.0002). By targeting SMAD7, miR-17-5p promoted nuclear translocation of β-catenin, enhanced expression of COL1A1 and finally facilitated the proliferation and differentiation of HMSC-bm cells. We also demonstrated that restoring expression of SMAD7 in HMSC-bm cells partially reversed the function of miR-17-5p. Together, our data suggested a theory that dysfunction of a network containing miR-17-5p, SMAD7 and β-catenin could contribute to ON pathogenesis. The present study prompts the potential clinical value of miR-17-5p in non-traumatic ON. Impaired stem cell proliferation and development may contribute to certain cases of bone degenerative disease. The blood vessel loss and resulting bone cell death associated with osteonecrosis (ON) can arise from trauma but in many cases the underlying pathology remains unknown. Researchers led by Weihua Xu and Shuhua Yang of the Huazhong University of Science and Technology in China showed that reduced expression of a particular regulatory RNA (miR-17-5p) may contribute to ON in some patients. The researchers examined mesenchymal stem cells (MSCs), which form diverse tissues including blood cells and bone. They observed reduced miR-17-5p levels in ON patients compared to osteoarthritis patients. This RNA has been shown to regulate cell growth and also appears to control bone formation by MSCs. Abnormalities in the miR-17-5p regulatory network may offer fruitful targets for treating ON.