Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease.
Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease.
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DOI：
10.1016/j.joca.2014.12.012
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发表时间：
2015-04
影响因子：
7
通讯作者：
Boulter, C. A.
中科院分区：
文献类型：
--
作者：
Roddy, K. A.;Boulter, C. A.
基质细胞蛋白NOV/CCN3与骨关节炎（OA）有关，小鼠NOV的靶向突变（Novdel3）导致关节异常。这项研究测试了关节内稳态是否需要NOV，以及它的破坏是否会导致关节退变。免疫组化检测成年小鼠关节中NOV的表达。通过x线、组织学和免疫组织化学对2、6和12月龄的Novdel3−/−和Novdel3+/+（野生型）雄性和雌性的关节进行了详细的比较。在成人膝关节关节软骨、半月板、滑膜和韧带附着部位的特定细胞中发现了NOV蛋白。Novdel3−/−男性在12个月时表现出严重的oa样病理（OARSI评分5.0±0.5,P < 0.001），影响关节的所有组织：关节软骨糜烂，半月板扩大，骨赘生长，韧带退行性变和纤维软骨扩张。软骨下硬化和与OA一致的细胞外基质组成的改变也可见。Novdel3+/+膝关节的关节软骨细胞密度在2 - 12月龄期间保持在恒定水平，而在Novdel3 - / -小鼠中则并非如此。与年龄和性别匹配的Novdel3+/+小鼠相比，在2个月时，Novdel3 - / -雄性和雌性的关节软骨密度显著增加，而在6和12个月时，Novdel3 - / -雄性和雌性的关节软骨密度均显著降低。NOV是维持关节软骨和关节内稳态所必需的，在衰老的Novdel3−/−雄性小鼠中，NOV的破坏会引起oa样疾病。
The matricellular protein NOV/CCN3, is implicated in osteoarthritis (OA) and targeted mutation of NOV in mice (Novdel3) leads to joint abnormalities. This investigation tested whether NOV is required for joint homeostasis and if its disruption causes joint degeneration. NOV expression in the adult mouse joint was characterized by immunohistochemistry. A detailed comparison of the joints of Novdel3−/− and Novdel3+/+ (wild-type) males and females at 2, 6 and 12 months of age was determined by X-ray, histology and immunohistochemistry. NOV protein was found in specific cells in articular cartilage, meniscus, synovium and ligament attachment sites in adult knees. Novdel3−/− males exhibited severe OA-like pathology at 12 months (OARSI score 5.0 ± 0.5, P < 0.001), affecting all tissues of the joint: erosion of the articular cartilage, meniscal enlargement, osteophytic outgrowths, ligament degeneration and expansion of fibrocartilage. Subchondral sclerosis and changes in extracellular matrix composition consistent with OA, were also seen. The density of articular cartilage cells in Novdel3+/+ knee joints is maintained at a constant level from 2 to 12 months of age whereas this is not the case in Novdel3−/− mice. Compared with age and sex-matched Novdel3+/+ mice, a significant increase in articular cartilage density was seen in Novdel3−/− males at 2 months, whereas a significant decrease was seen at 6 and 12 months in both Novdel3−/− males and females. NOV is required for the maintenance of articular cartilage and for joint homeostasis, with disruption of NOV in ageing Novdel3−/− male mice causing OA-like disease.
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DOI：
10.1038/jid.2010.15
发表时间：
2010-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.2
作者：
Kawaki, Harumi;Kubota, Satoshi;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu
影响因子：
4.6
作者：
Ivkovic, S;Yoon, BS;Lyons, KM
通讯作者：
Lyons, KM
影响因子：
7
作者：
Little, B;Ghosh, P;Rose, R
通讯作者：
Rose, R
影响因子：
4.1
作者：
Janune, Danilo;Kubota, Satoshi;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu