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., TNFα, 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.
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