MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis
Department of Cell Biology
Animals; Cartilage, Articular; Cells, Cultured; Chondrocytes; Humans; MicroRNAs; Neural Pathways; Neuroglia; Osteoarthritis; Osteoarthritis, Knee; Pain; Rats; Synovial Membrane; Transfection
Because miR-146a is linked to osteoarthritis (OA) and cartilage degeneration is associated with pain, we have characterized the functional role of miR-146a in the regulation of human articular cartilage homeostasis and pain-related factors. Expression of miRNA 146a was analyzed in human articular cartilage and synovium, as well as in dorsal root ganglia (DRG) and spinal cord from a rat model for OA-related pain assessment. The functional effects of miR-146a on human chondrocytic, synovial, and microglia cells were studied in cells transfected with miR-146a. Using real-time PCR, we assessed the expression of chondrocyte metabolism-related genes in chondrocytes, genes for inflammatory factors in synovial cells, as well as pain-related proteins and ion channels in microglial cells. Previous studies showed that miR-146a is significantly upregulated in human peripheral knee OA joint tissues. Transfection of synthetic miR-146a significantly suppresses extracellular matrix-associated proteins (e.g., Aggrecan, MMP-13, ADAMTS-5, collagen II) in human knee joint chondrocytes and regulates inflammatory cytokines in synovial cells from human knee joints. In contrast, miR-146a is expressed at reduced levels in DRGs and dorsal horn of the spinal cords isolated from rats experiencing OA-induced pain. Exogenous supplementation of synthetic miR-146a significantly modulates inflammatory cytokines and pain-related molecules (e.g., TNFalpha, COX-2, iNOS, IL-6, IL8, RANTS and ion channel, TRPV1) in human glial cells. Our findings suggest that miR-146a controls knee joint homeostasis and OA-associated algesia by balancing inflammatory responses in cartilage and synovium with pain-related factors in glial cells. Hence, miR-146a may be useful for the treatment of both cartilage regeneration and pain symptoms caused by OA.
DOI of Published Version
Gene. 2011 Jul 1;480(1-2):34-41. Epub 2011 Mar 21. Link to article on publisher's site
Li, Xin; Gibson, Gary; Kim, Jae-Sung; Kroin, Jeffrey S.; Xu, Shunbin; Van Wijnen, Andre J.; and Im, Hee-Jeong, "MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis" (2011). Stein, Stein, Lian, vanWijnen Lab Publications. 261.