Matrix metalloproteinase induction by relaxin causes cartilage matrix degradation in target synovial joints.
Matrix metalloproteinase induction by relaxin causes cartilage matrix degradation in target synovial joints.
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DOI：
10.1111/j.1749-6632.2009.03830.x
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发表时间：
2009-04
影响因子：
5.2
通讯作者：
Uston K
中科院分区：
文献类型：
--
作者：
Kapila S;Wang W;Uston K
我们的长期目标是了解松弛素和雌激素可能导致关节疾病的机制，特别是那些困扰纤维软骨颞下颌关节（TMJ）。之前，我们发现松弛素对基质金属蛋白酶（MMP）家族的组织降解酶产生剂量依赖性诱导，特别是在TMJ纤维软骨的细胞分离物和组织外植体中的MMP-1（胶原酶-1），-3（stromelysin-1），-9（92-kDa-明胶酶）和-13（胶原酶-3）。这些MMP的诱导伴随着胶原蛋白和糖胺聚糖（GAG）的损失，这被泛MMP抑制剂阻断。我们还发现用β-雌二醇或松弛素或两种激素一起治疗的卵巢切除兔的TMJ盘中胶原和GAG的靶向体内损失。孕酮减弱松弛素和雌激素诱导的MMPs和基质丢失。TMJ纤维软骨基质成分的调制这些激素是类似的观察到的耻骨联合，并从膝关节半月板不同。表现出最大的MMPs调节和基质损失的两个靶组织，即TMJ椎间盘和耻骨联合，具有与膝关节半月板细胞不同的雌激素受体（ER）-α和-β、松弛素-1受体（RXFP 1，LGR 7）和INSL 3受体（RXFP 2，LGR 8）的相似表达谱。这些发现表明了一种新的模型，通过选择MMPs介导的诱导特定关节软骨的靶向组织周转。
Our long-term goal is to understand the mechanisms by which relaxin and estrogen potentially contribute to joint diseases particularly those afflicting the fibrocartilaginous temporomandibular joint (TMJ). Previously, we showed that relaxin produces a dose-dependent induction of tissue degrading enzymes of the matrix metalloproteinase (MMP) family, specifically MMP-1 (collagenase-1), −3 (stromelysin-1), −9 (92-kDa-gelatinase) and −13 (collagenase-3) in cell isolates and tissue explants from TMJ fibrocartilage. The induction of these MMPs is accompanied by loss of collagen and glycosaminoglycans (GAGs), which was blocked by a pan-MMP inhibitor. We also found the targeted in vivo loss of collagen and GAGs in TMJ discs of ovariectomized rabbits treated with β-estradiol or relaxin or both hormones together. Progesterone attenuated the induction of MMPs and matrix loss by relaxin and estrogen. The modulation of matrix composition in TMJ fibrocartilage by these hormones was similar to that observed in the pubic symphysis, and differed from that of the knee meniscus. The two target tissues showing the greatest modulation of MMPs and matrix loss, namely the TMJ disc and pubic symphysis, had similar expression profiles of the estrogen receptors (ER)-α and –β, relaxin-1 receptor (RXFP1, LGR7), and INSL3 receptor (RXFP2, LGR8) that differed from those in cells from the knee meniscus. These findings suggest a novel model for targeted tissue turnover of cartilages of specific joints through hormone-mediated induction of select MMPs.
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影响因子：
4.7
作者：
Di Nezza, LA;Jobling, T;Salamonsen, LA
通讯作者：
Salamonsen, LA
影响因子：
5.8
作者：
Hwang, JJ;Macinga, D;Rorke, EA
通讯作者：
Rorke, EA
影响因子：
56.9
作者：
Hsu, SY;Nakabayashi, K;Hsueh, AJW
通讯作者：
Hsueh, AJW
影响因子：
8
作者：
Stevens, T. A.;Meech, R.
通讯作者：
Meech, R.
影响因子：
4.4
作者：
Marin-Castaño, ME;Elliot, SJ;Cousins, SW
通讯作者：
Cousins, SW