Effects of a metalloproteinase inhibitor on osteochondral angiogenesis, chondropathy and pain behavior in a rat model of osteoarthritis.
Effects of a metalloproteinase inhibitor on osteochondral angiogenesis, chondropathy and pain behavior in a rat model of osteoarthritis.
复制标题
DOI：
10.1016/j.joca.2009.12.006
复制
发表时间：
2010-04
影响因子：
7
通讯作者：
Maciewicz, R. A.
中科院分区：
文献类型：
--
作者：
Mapp, P. I.;Walsh, D. A.;Bowyer, J.;Maciewicz, R. A.
目的：研究基质金属蛋白酶(MMP)抑制剂对半月板横断(MNX)骨关节炎(OA)大鼠关节病理和疼痛行为的影响，并评价结构性疾病改变对症状改善的作用。雄性Lewis大鼠切断内侧副韧带(MNX)或不切断半月板(Sham)，造成骨关节炎病理改变。MNX动物从第1天开始口服等效MMP2、8、9、12、13抑制剂(0.25、1和5 mg/kg/d)或赋形剂。通过甲苯胺蓝染色的全膝关节冠状切片和丧失能力的负重不对称来评价软骨病变、骨赘形成和骨软骨血管。用单因素方差分析(ANOVA)和关联度作为Spearman‘s相关系数来评估组内差异。使用基质金属蛋白酶抑制剂的治疗从第14天起减少了负重不对称性，并减轻了软骨病变(P均<0.05)。与假手术组相比，MNX组的骨软骨血管数量增加(P<0.001.0 5)，并被基质金属蛋白酶抑制剂治疗剂量依赖性地减少(r=−0.89，P<0.0 5)。骨软骨血管减少和软骨病变与负重不对称性的改善有关(P均<0.05)。在这里，我们表明，使用基质金属蛋白酶抑制剂治疗可以减少关节损伤、骨软骨血管生成和疼痛的行为证据。骨软骨血管生成与疼痛行为之间的关系可以通过血管周围神经生长或骨软骨完整性丧失后软骨下神经的刺激来解释。我们的数据表明，靶向血管生成可能在治疗与骨性关节炎结构损伤相关的疼痛方面有实用价值。
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. 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. 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). 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.
登录
查看更多内容
影响因子：
--
作者：
Hwang, Jennifer;Bae, Won C.;Shieu, Wendy;Lewis, Chad W.;Bugbee, William D.;Sah, Robert L.
通讯作者：
Sah, Robert L.
影响因子：
--
作者：
Hunter, David J.;Zhang, Yuqing;Felson, David T.
通讯作者：
Felson, David T.
影响因子：
7
作者：
Mihara, M.;Higo, S.;Saito, K.
通讯作者：
Saito, K.
影响因子：
--
作者：
Felson, David T.;Niu, Jingbo;Aliabadi, Piran
通讯作者：
Aliabadi, Piran
影响因子：
15.9
作者：
Billinghurst, RC;Dahlberg, L;Poole, AR
通讯作者：
Poole, AR