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

143 Citations (Scopus)

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
Externally publishedYes

Fingerprint

MicroRNAs
Osteoarthritis
Pain
Knee Joint
Chondrocytes
Cartilage
Synovial Membrane
Knee Osteoarthritis
Articular Cartilage
Ion Channels
Neuroglia
Homeostasis
Cytokines
Aggrecans
Extracellular Matrix Proteins
Diagnosis-Related Groups
Spinal Ganglia
Microglia
Pain Measurement
Matrix Metalloproteinases

Keywords

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

ASJC Scopus subject areas

  • Genetics

Cite this

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

MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis. / Li, Xin; Gibson, Gary; Kim, Jae Sung; Kroin, Jeffrey; Xu, Shunbin; van Wijnen, Andre J; Im, Hee Jeong.

In: Gene, Vol. 480, No. 1-2, 01.07.2011, p. 34-41.

Research output: Contribution to journalArticle

Li, X, Gibson, G, Kim, JS, Kroin, J, Xu, S, van Wijnen, AJ & Im, HJ 2011, 'MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis', Gene, vol. 480, no. 1-2, pp. 34-41. https://doi.org/10.1016/j.gene.2011.03.003
Li X, Gibson G, Kim JS, Kroin J, Xu S, van Wijnen AJ et al. MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis. Gene. 2011 Jul 1;480(1-2):34-41. https://doi.org/10.1016/j.gene.2011.03.003
Li, Xin ; Gibson, Gary ; Kim, Jae Sung ; Kroin, Jeffrey ; Xu, Shunbin ; van Wijnen, Andre J ; Im, Hee Jeong. / MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis. In: Gene. 2011 ; Vol. 480, No. 1-2. pp. 34-41.
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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.",
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