Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1

Abstract

Osteoarthritis (OA) is a degenerative disease characterized by deterioration of articular cartilage. Recent studies have demonstrated the importance of some microRNAs in cartilage damage. The aim of this study was to identify and characterize the expression of microRNA-634 (miR-634) in normal and OA chondrocytes, and to determine its role in OA pathogenesis. Human normal and OA chondrocytes obtained from patients were cultured in vitro. Transfection with miR-634 mimic or inhibitor was employed to investigate the effect of miR-634 on chondrocyte survival and matrix synthesis, and to identify miR-634 target. The results indicated that miR-634 was expressed at lower level in high grade OA chondrocyte compared with normal chondrocytes. Overexpression of miR-634 could inhibit cell survival and matrix synthesis in high grade OA chondrocytes. Furthermore, miR-634 targeted PIK3R1 gene that encodes the regulatory subunit 1 of class I PI3K (p85α) and exerted its inhibitory effect on the phosphorylation of Akt, mTOR, and S6 signal molecules in high grade OA chondrocytes. Therefore, the data suggested that miR-634 could suppress survival and matrix synthesis of high grade OA chondrocytes through targeting PIK3R1 gene to modulate the PI3K/Akt/S6 and PI3K/Akt/mTOR/S6 axes, with important implication for validating miR-634 as a potential target for OA therapy.

Knockdown MiR-302b Alleviates LPS-Induced Injury by Targeting Smad3 in C28/I2 Chondrocytic Cells

“…OA is characterized by deterioration of functions of chondrocytes, an integral part of articular cartilage, subchondral bone and joint margins [1]. Studies have shown that proteolytic enzymes such as matrix metalloproteinases (MMP), secreted by chondrocytes are involved in degradation of cartilage [2, 3]. The pathogenesis of OA is a multifactorial disorder with genetic, developmental, biochemical and biomechanical factors contributing to the development of disease process [1, 3].…”

“…Osteoarthritis (OA) is one of the commonest chronic degenerative diseases, especially among the old age people, seriously affects the quality of life of the affected patients [1, 2]. OA is characterized by deterioration of functions of chondrocytes, an integral part of articular cartilage, subchondral bone and joint margins [1].…”

MiR-15a-5p regulates viability and matrix degradation of human osteoarthritis chondrocytes <i>via</i> targeting VEGFA

“…Several recent studies demonstrated their importance in maintaining cartilage homeostasis and their effects on promoting the pathogenesis of OA. For instance, it was claimed in 2016 by Xu Cui and his group that by targeting PIK3R1, overexpression of miR-634 can suppress survival and matrix synthesis of human osteoarthritis chondrocytes (2). It is illustrated by Tadahiro Sakai and his colleagues that miR125b plays a pivotal role in regulating expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes (3).…”

Chondrogenic Potential of Peripheral Blood Derived Mesenchymal Stem Cells Seeded on Demineralized Cancellous Bone Scaffolds

“…The reason of the discrepancies between mRNA and protein expression in our study might be due to the posttranscriptional regulation of the mRNA which has been reported previously12. For instance, microRNAs were known to regulate the target mRNA translation either through translational silencing of the mRNA or degradation of the mRNA in osteoarthritis and chondrogenesis1314. It should be noted that there was a tendency of increased COL 2 production of both MSCs with time, thus it is reasonable to expect the same even higher level of COL 2 of MSCs groups compared to that of ACCs with longer culturing time or in vivo transplantation.…”