Ageing related deficiency of miR-708-5p in osteoarthritic cartilage lesions [RNA]
Aging is a major risk factors for osteoarthritis (OA), and cartilage of the elder are more sensitive to mechanical loading stress. Recently, cartilage progenitor cells (CPCs) arose much interests due to its important role in maintaining cartilage homeostasis. However, the potential mechanism of increased sensitivity to mechanical stress in CPCs has not been elucidated. The aim of this study was to investigate the potential links between aging and age-related OA through establish CPCs replicative senescence model and fluid flow shear stress (FFSS) stimulated degeneration model. Small RNA and mRNA sequence were conducted to investigate miRNA-related mechanisms in this process. By gain-and-lost strategy we investigated the age-related miRNAs and their impacts on exacerbating the progression of biomechanical stimulated TMJ-OA. miR-708-5p was identified as age-related miRNA in CPCs, and TLR4 was identified as its direct target through luciferase report assay. Age-related miR-708-5p deficiency increased sensitivity of CPCs for exposure to FFSS by liberating TLR4 expression. Intra-articular delivery agomiR-708-5p alleviated TMJ osteoarthritic cartilage lesions in mice. In conclusion, age-related miR-708-5p deficiency increases the sensitivity to mechanical loading stress and promotes CPCs senescence like degeneration via TLR4. Overall design: To investigated the common mechanism between replicative senescence and abberant mechanical stress induced senescence like degeneration of cartilage progenitor cells (CPCs), we established replicative senescence model and flow fluid shear stress induced degeneration model of CPCs in vitro. We choosed CPCs of Passage 3 as control group, CPCs of passage 9 as replicative senescence group, and FFSS treated P3 CPCs as FFSS induced degeneration group. Then we performed RNA-seq and miRNA-seq .