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dc.contributor.authorWalsh, David A
dc.date.accessioned2022-05-09T10:58:53Z
dc.date.available2022-05-09T10:58:53Z
dc.date.issued2010-04
dc.identifier.citationMapp, PI, Walsh, DA, Bowyer, J & Maciewicz, RA 2010, ‘Effects of a metalloproteinase inhibitor on osteochondral angiogenesis, chondropathy and pain behavior in a rat model of osteoarthritis’, Osteoarthritis and Cartilage, vol. 18, no. 4, pp. 593–600en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12904/15405
dc.description.abstractObjective: To investigate the effects of a matrix metalloproteinase (MMP) inhibitor on joint pathology and pain behavior in the rat meniscal transection (MNX) model of osteoarthritis (OA) and evaluate which aspects of structural disease modification contribute to symptom improvement. Methods: OA pathology was induced in male Lewis rats, by transecting the medial collateral ligament with (MNX) or without (SHAM) a full thickness cut through the meniscus. MNX animals were orally administered an equipotent MMP 2, 8, 9, 12, 13 inhibitor (0.25, 1 and 5 mg/kg/day) or vehicle from day 1. Chondropathy, osteophytosis, osteochondral vascularity were assessed from toluidine blue stained coronal sections of the total knee joint and weight-bearing asymmetry by incapacitance. Group differences were evaluated using 1-way analysis of variance (ANOVA) and associations as Spearman's correlation coefficients. Results: Treatment with the MMP inhibitor reduced weight-bearing asymmetry from day 14 onwards, and attenuated chondropathy (both P<0.05). Osteochondral vascularity was elevated in MNX compared with SHAM-operated animals (P<0.001) and reduced, dose-dependently, by MMP inhibitor treatment (r=-0.89, P<0.05). Reduced osteochondral vascularity and chondropathy were associated with the amelioration of weight-bearing asymmetry (both P<0.05). Conclusion: Here we show that treatment with a MMP inhibitor reduces joint damage, osteochondral angiogenesis and behavioral evidence of pain. The association between osteochondral angiogenesis and pain behavior may be explained by perivascular nerve growth or stimulation of subchondral nerves following loss of osteochondral integrity. Our data suggest that targeting angiogenesis may have utility in the treatment of pain associated with structural damage in OA.
dc.description.urihttps://www.oarsijournal.com/article/S1063-4584(09)00328-8/fulltexten_US
dc.publisherOsteoarthritis and Cartilageen_US
dc.subjectOsteoarthritisen_US
dc.subjectRat modelen_US
dc.subjectPain behavioren_US
dc.subjectChondropathyen_US
dc.subjectOsteochondral angiogenesisen_US
dc.titleEffects of a metalloproteinase inhibitor on osteochondral angiogenesis, chondropathy and pain behavior in a rat model of osteoarthritisen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecord10.1016/j.joca.2009.12.006en_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.dateFOA2022-05-09T10:58:53Z
refterms.panelUnspecifieden_US
refterms.dateFirstOnline2010-01
html.description.abstractObjective: To investigate the effects of a matrix metalloproteinase (MMP) inhibitor on joint pathology and pain behavior in the rat meniscal transection (MNX) model of osteoarthritis (OA) and evaluate which aspects of structural disease modification contribute to symptom improvement. Methods: OA pathology was induced in male Lewis rats, by transecting the medial collateral ligament with (MNX) or without (SHAM) a full thickness cut through the meniscus. MNX animals were orally administered an equipotent MMP 2, 8, 9, 12, 13 inhibitor (0.25, 1 and 5 mg/kg/day) or vehicle from day 1. Chondropathy, osteophytosis, osteochondral vascularity were assessed from toluidine blue stained coronal sections of the total knee joint and weight-bearing asymmetry by incapacitance. Group differences were evaluated using 1-way analysis of variance (ANOVA) and associations as Spearman's correlation coefficients. Results: Treatment with the MMP inhibitor reduced weight-bearing asymmetry from day 14 onwards, and attenuated chondropathy (both P<0.05). Osteochondral vascularity was elevated in MNX compared with SHAM-operated animals (P<0.001) and reduced, dose-dependently, by MMP inhibitor treatment (r=-0.89, P<0.05). Reduced osteochondral vascularity and chondropathy were associated with the amelioration of weight-bearing asymmetry (both P<0.05). Conclusion: Here we show that treatment with a MMP inhibitor reduces joint damage, osteochondral angiogenesis and behavioral evidence of pain. The association between osteochondral angiogenesis and pain behavior may be explained by perivascular nerve growth or stimulation of subchondral nerves following loss of osteochondral integrity. Our data suggest that targeting angiogenesis may have utility in the treatment of pain associated with structural damage in OA.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


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