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MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis
Xin Li1, Gary Gibson, Jae-Sung Kim
1Department of Biochemistry, Rush University Medical Center, 1735 W. Harrison, Chicago, IL 60612, USA.
Abstract:
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.
Insights
MicroRNA-146a (miR-146a) plays a key role in osteoarthritis (OA) by regulating cartilage health and pain. This study shows miR-146a can treat OA-related cartilage degeneration and pain.
Area of Science:
- Biomedical Science
- Molecular Biology
- Pain Research
Background:
- Osteoarthritis (OA) is characterized by cartilage degeneration and pain.
- MicroRNA-146a (miR-146a) has been implicated in OA pathogenesis.
- The precise role of miR-146a in cartilage homeostasis and pain signaling remains to be fully elucidated.
Purpose of the Study:
- To investigate the functional role of miR-146a in regulating human articular cartilage homeostasis.
- To examine the impact of miR-146a on pain-related factors in the context of OA.
- To assess the therapeutic potential of miR-146a for OA treatment.
Main Methods:
- Analysis of miR-146a expression in human OA tissues and a rat OA pain model.
- Functional studies of miR-146a in human chondrocytic, synovial, and microglial cells.
- Assessment of gene and protein expression related to cartilage metabolism, inflammation, and pain.
Main Results:
- miR-146a upregulation in human OA tissues.
- miR-146a transfection suppressed extracellular matrix genes in chondrocytes and modulated inflammatory cytokines in synovial cells.
- Reduced miR-146a levels in DRGs and spinal cords of OA pain model rats.
- Exogenous miR-146a modulated inflammatory cytokines and pain-related molecules in glial cells.
Conclusions:
- miR-146a is a critical regulator of knee joint homeostasis and OA-associated pain (algesia).
- miR-146a balances inflammatory responses in cartilage and synovium with pain signaling in glial cells.
- miR-146a holds potential for treating both cartilage regeneration and pain in OA.
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