Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis.
Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis.
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DOI：
10.1186/ar4423
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发表时间：
2013
影响因子：
4.9
通讯作者：
Illges H
中科院分区：
文献类型：
--
作者：
Singh A;Rajasekaran N;Hartenstein B;Szabowski S;Gajda M;Angel P;Bräuer R;Illges H
基质金属蛋白酶(MMPs)在组织重塑中起重要作用。在这里，我们研究了胶原酶-3(MMP-13)在抗体诱导的关节炎中的作用。在本研究中，我们采用了K/BxN血清诱导的关节炎模型。给C57BL/6野生型(WT)和基质金属蛋白酶-13缺陷(MMP13-/-)小鼠腹腔注射2 0 0μL K/BxN血清，诱导小鼠关节炎。通过测量踝关节肿胀来评估关节炎。在实验过程中，每隔一天处死一次小鼠，进行踝关节的组织学检查。对踝关节切片进行组织学检查，观察炎性细胞的浸润、血管疙瘩的形成和骨/软骨的破坏情况。采用半定量聚合酶链式反应技术检测未治疗组和K/BxN血清注射组小鼠踝关节组织中基质金属蛋白酶-13的表达水平。这项研究表明，基质金属蛋白酶-13是一种炎症调节因子。我们观察到，在K/BxN血清诱导的关节炎期间，WT小鼠的踝关节中MMP-13的表达增加，而K/BxN血清治疗的WT小鼠和MMP-13-/-小鼠发生的进行性关节炎的发病情况相似。然而，在整个关节炎期间，MMP-13-/-小鼠的疾病显著减少。WT小鼠踝关节表现为严重的关节破坏，并伴有广泛的炎症和软骨、骨的侵蚀。相比之下，通过临床和组织学评分方法分析，MMP-13-/-小鼠的关节炎严重程度显著降低(50%至60%)。基质金属蛋白酶-13缺乏可抑制局部炎症反应。因此，基质金属蛋白酶-13在关节炎的发病机制中具有一定的作用，提示基质金属蛋白酶-13是一个潜在的治疗靶点。
Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis. For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13–/–) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacrificed every second day for histological examination of the ankle joints. Ankle sections were evaluated histologically for infiltration of inflammatory cells, pannus tissue formation and bone/cartilage destruction. Semi-quantitative PCR was used to determine MMP-13 expression levels in ankle joints of untreated and K/BxN serum-injected mice. This study shows that MMP-13 is a regulator of inflammation. We observed increased expression of MMP-13 in ankle joints of WT mice during K/BxN serum-induced arthritis and both K/BxN serum-treated WT and MMP-13–/– mice developed progressive arthritis with a similar onset. However, MMP-13–/– mice showed significantly reduced disease over the whole arthritic period. Ankle joints of WT mice showed severe joint destruction with extensive inflammation and erosion of cartilage and bone. In contrast, MMP-13–/– mice displayed significantly decreased severity of arthritis (50% to 60%) as analyzed by clinical and histological scoring methods. MMP-13 deficiency acts to suppress the local inflammatory responses. Therefore, MMP-13 has a role in the pathogenesis of arthritis, suggesting MMP-13 is a potential therapeutic target.
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影响因子：
4.9
作者：
Wang M;Sampson ER;Jin H;Li J;Ke QH;Im HJ;Chen D
通讯作者：
Chen D
影响因子：
4.8
作者：
Borden, P;Solymar, D;Heller, RA
通讯作者：
Heller, RA
影响因子：
4.6
作者：
Stickens, D;Behonick, DJ;Werb, Z
通讯作者：
Werb, Z
影响因子：
--
作者：
Little, C. B.;Barai, A.;Burkhardt, D.;Smith, S. M.;Fosang, A. J.;Werb, Z.;Shah, M.;Thompson, E. W.
通讯作者：
Thompson, E. W.
影响因子：
64.5
作者：
Kouskoff, V;Korganow, AS;Mathis, D
通讯作者：
Mathis, D