miRNA-103 promotes chondrocyte apoptosis by down-regulation of Sphingosine kinase-1 and ameliorates PI3K/AKT pathway in osteoarthritis.

OBJECTIVES

The aim of the present study was to determine the effects of miRNA-103 on chondrocyte apoptosis and molecular mechanisms in osteoarthritis (OA) progression.

METHODS

The cell proliferation, apoptosis, and recovery ability were measured by cell counting kit-8 (CCK-8), flow cytometry, and wound healing assays. The interaction of miRNA-103 and Sphingosine kinase-1 (SPHK1) were determined by using luciferase reporter assay. The expression of mRNA and proteins were measured by qRT-PCR and Western blot. OA rat model was established by surgery stimulation.

RESULTS

miRNA-103 expression was significantly increased in the cartilage of OA patients and surgery-induced OA rat models. miRNA-103 transfection into primary rat chondrocytes reduced SPHK1 expression, induced apoptosis, inhibited cell proliferation, and impeded scratch assay wound closure. Moreover, expression of total AKT, and p-AKT were significantly reduced in miRNA-103-overexpressing chondrocytes while SPHK1 up-regulation increased the expression of phosphatidylinsitol-3-kinase (PI3K) and p-AKT, and reversed the proliferation suppression induced by the miRNA-103 mimic.

CONCLUSIONS

Our studies suggest that miRNA-103 contributes to chondrocyte apoptosis, promoting OA progression by down-regulation of PI3K/AKT pathway through the reduction in SPHK1 activity.