MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis
dc.contributor.author | Li, Xin | |
dc.contributor.author | Gibson, Gary | |
dc.contributor.author | Kim, Jae-Sung | |
dc.contributor.author | Kroin, Jeffrey S. | |
dc.contributor.author | Xu, Shunbin | |
dc.contributor.author | Van Wijnen, Andre J. | |
dc.contributor.author | Im, Hee-Jeong | |
dc.date | 2022-08-11T08:10:57.000 | |
dc.date.accessioned | 2022-08-23T17:26:14Z | |
dc.date.available | 2022-08-23T17:26:14Z | |
dc.date.issued | 2011-07-15 | |
dc.date.submitted | 2012-05-10 | |
dc.identifier.citation | Gene. 2011 Jul 1;480(1-2):34-41. Epub 2011 Mar 21. <a href="http://dx.doi.org/10.1016/j.gene.2011.03.003">Link to article on publisher's site</a> | |
dc.identifier.issn | 0378-1119 (Linking) | |
dc.identifier.doi | 10.1016/j.gene.2011.03.003 | |
dc.identifier.pmid | 21397669 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/49592 | |
dc.description.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., 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. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21397669&dopt=Abstract">Link to Article in PubMed</a> | |
dc.relation.url | http://dx.doi.org/10.1016/j.gene.2011.03.003 | |
dc.subject | Animals | |
dc.subject | Cartilage, Articular | |
dc.subject | Cells, Cultured | |
dc.subject | Chondrocytes | |
dc.subject | Humans | |
dc.subject | MicroRNAs | |
dc.subject | Neural Pathways | |
dc.subject | Neuroglia | |
dc.subject | Osteoarthritis | |
dc.subject | Osteoarthritis, Knee | |
dc.subject | Pain | |
dc.subject | Rats | |
dc.subject | Synovial Membrane | |
dc.subject | Transfection | |
dc.subject | Cell Biology | |
dc.title | MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis | |
dc.type | Journal Article | |
dc.source.journaltitle | Gene | |
dc.source.volume | 480 | |
dc.source.issue | 1-2 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/stein/261 | |
dc.identifier.contextkey | 2838653 | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | stein/261 | |
dc.contributor.department | Department of Cell Biology | |
dc.source.pages | 34-41 |