Hyaluronan injection in murine osteoarthritis prevents TGFbeta 1-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism.
Hyaluronan injection in murine osteoarthritis prevents TGFbeta 1-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism.
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DOI：
10.1186/ar3887
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发表时间：
2012-06-21
影响因子：
4.9
通讯作者：
Plaas A
中科院分区：
文献类型：
--
作者：
Li J;Gorski DJ;Anemaet W;Velasco J;Takeuchi J;Sandy JD;Plaas A
关节内注射透明质酸(HA)改善关节病理的机制尚不清楚。动物研究表明，HA可以减少滑膜活化、关节周围纤维化和软骨侵蚀，但其对不同细胞类型的具体作用尚不清楚。我们使用了小鼠骨关节炎(OA)的TTR(TGFbeta1注射和跑步机跑步)模型，该模型表现出许多OA样的变化，包括滑膜的激活，以检测关节内HA的组织特异性效应。用全身显像法研究了氟化羟基磷灰石从关节中的清除动力学。对幼稚和治疗后的膝关节进行了软骨侵蚀、半月板损伤和纤维化的大体检查。软骨用藏红O染色，滑膜用苏木精-伊红染色进行定量组织病理学检查。用定量聚合酶链式反应检测Acan、Col1a1、Col2a1、Col3a1、Col5a1、Col10a1、Adamts5和Mmp13基因在关节组织中的表达。免疫组织化学方法检测集聚糖、I型、II型、II型、V型和X型胶原、ADAMTS5和MMP13的丰度和分布。注射HA在小鼠膝关节的半衰期不到2小时。在组织水平上，HA防止半月板/滑膜新生血管和纤维化，并在野生型小鼠中保持关节软骨的完整性，但在CD44基因敲除小鼠中则不然。HA可增强软骨形成基因和蛋白的表达，阻断软骨/软骨下骨中成纤维/降解基因和蛋白的表达，而阻断半月板/滑膜中成软骨基因和蛋白的激活。在所有部位，它都降低了Mmp13的表达/蛋白，并阻止了Adamts5的表达，但不能阻止其在滑膜衬里的蛋白丰度。在注射TGFbeta1后24小时注射HA，可抑制在跑台运动后出现的OA样关节改变的级联。在机制上，注射HA的组织保护作用被CD44消融所消除，提示注射的HA与CD44的相互作用是其保护关节组织重塑和退变的核心作用。
The mechanism by which intra-articular injection of hyaluronan (HA) ameliorates joint pathology is unknown. Animal studies have shown that HA can reduce synovial activation, periarticular fibrosis and cartilage erosion; however, its specific effects on the different cell types involved remain unclear. We have used the TTR (TGFbeta1 injection and Treadmill Running) model of murine osteoarthritis (OA), which exhibits many OA-like changes, including synovial activation, to examine in vivo tissue-specific effects of intra-articular HA. The kinetics of clearance of fluorotagged HA from joints was examined with whole-body imaging. Naïve and treated knee joints were examined macroscopically for cartilage erosion, meniscal damage and fibrosis. Quantitative histopathology was done with Safranin O for cartilage and with Hematoxylin & Eosin for synovium. Gene expression in joint tissues for Acan, Col1a1, Col2a1, Col3a1, Col5a1, Col10a1, Adamts5 and Mmp13 was done by quantitative PCR. The abundance and distribution of aggrecan, collagen types I, II, III, V and X, ADAMTS5 and MMP13 were examined by immunohistochemistry. Injected HA showed a half-life of less than 2 h in the murine knee joint. At the tissue level, HA protected against neovascularization and fibrosis of the meniscus/synovium and maintained articular cartilage integrity in wild-type but not in Cd44 knockout mice. HA injection enhanced the expression of chondrogenic genes and proteins and blocked that of fibrogenic/degradative genes and proteins in cartilage/subchondral bone, whereas it blocked activation of both groups in meniscus/synovium. In all locations it reduced the expression/protein for Mmp13 and blocked Adamts5 expression but not its protein abundance in the synovial lining. The injection of HA, 24 h after TGFbeta1 injection, inhibited the cascade of OA-like joint changes seen after treadmill use in the TTR model of OA. In terms of mechanism, tissue protection by HA injection was abrogated by Cd44 ablation, suggesting that interaction of the injected HA with CD44 is central to its protective effects on joint tissue remodeling and degeneration in OA progression.
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影响因子：
--
作者：
Asari, A;Miyauchi, S;Uchiyama, K
通讯作者：
Uchiyama, K
影响因子：
2.8
作者：
Murray, Dianne H.;Bush, Peter G.;Brenkel, Ivan J.;Hall, Andrew C.
通讯作者：
Hall, Andrew C.
影响因子：
4.9
作者：
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通讯作者：
Kjaer, Michael
影响因子：
2.8
作者：
Julovi, Sohel M.;Ito, Hiromu;Nakamura, Takashi
通讯作者：
Nakamura, Takashi
影响因子：
1.5
作者：
Frazier, Kendall;Thomas, Roberta;Gellibert, Francoise
通讯作者：
Gellibert, Francoise