Exp Mol Med.  2014 Jul;46(7):e107. 10.1038/emm.2014.43.

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

• Jia J
• Feng X
• Xu W
• Yang S
• Zhang Q
• Liu X
• Feng Y
• Dai Z

• KMID: 2155372
• DOI: http://doi.org/10.1038/emm.2014.43

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 beta-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 beta-catenin could contribute to ON pathogenesis. The present study prompts the potential clinical value of miR-17-5p in non-traumatic ON.

MeSH Terms

Adult
Base Sequence
Bone Morphogenetic Protein 2/metabolism
Cell Differentiation
Cell Line
Cell Proliferation
Female
*Gene Expression Regulation
Humans
Male
MicroRNAs/genetics/*metabolism
Middle Aged
Osteoarthritis/genetics/metabolism/pathology
Osteoblasts/*cytology/metabolism/*pathology
Osteogenesis
Osteonecrosis/*genetics/metabolism/pathology
Signal Transduction
Smad7 Protein/*genetics/metabolism
beta Catenin/metabolism
Bone Morphogenetic Protein 2
MicroRNAs
Smad7 Protein
beta Catenin