MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis

Xin Li, Gary Gibson, Jae Sung Kim, Jeffrey Kroin, Shunbin Xu, Andre J. van Wijnen, Hee Jeong Im

Research output: Contribution to journalArticle

145 Scopus citations

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, synovialm 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.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalGene
Volume480
Issue number1-2
DOIs
StatePublished - Jul 1 2011

Keywords

  • Chondrocyte
  • Glial cells
  • MiR-146a
  • Osteoarthritis
  • Pain
  • Synovial cells

ASJC Scopus subject areas

  • Genetics

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    Li, X., Gibson, G., Kim, J. S., Kroin, J., Xu, S., van Wijnen, A. J., & Im, H. J. (2011). MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis. Gene, 480(1-2), 34-41. https://doi.org/10.1016/j.gene.2011.03.003