Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice.
Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice.
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关节软骨细胞中 Runx2 的缺失可减缓成年小鼠 DMM 诱导的骨关节炎的进展
DOI：
10.1038/s41598-017-02490-w
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发表时间：
2017-05-24
影响因子：
4.6
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Liao L;Zhang S;Gu J;Takarada T;Yoneda Y;Huang J;Zhao L;Oh CD;Li J;Wang B;Wang M;Chen D
Runx 2可能在骨关节炎（OA）的发生发展中起重要作用。然而，Runx 2在成年小鼠关节软骨细胞功能和OA发展中的具体作用尚未完全确定。在这项研究中，我们对12周龄的小鼠进行了内侧半月板（DMM）不稳定手术，以诱导成年Runx 2小鼠的OA。
Agc1CreER
小鼠，其中通过在8周龄时施用他莫昔芬在表达聚集蛋白聚糖的软骨细胞中特异性缺失Runx 2。在术后8周和12周采集膝关节样本，并通过组织学、组织形态计量学和显微计算机断层扫描（μCT）进行分析。我们的研究结果表明，Cre阴性对照小鼠DMM手术后观察到严重的OA样缺陷，包括关节软骨退化和软骨下硬化，而Runx 2小鼠的缺陷明显改善
Agc1CreER
KO小鼠。免疫组化（IHC）结果显示，Runx 2中MMP 13的表达显著降低，
Agc1CreER
KO小鼠与Cre阴性对照小鼠相比。定量逆转录PCR（qRT-PCR）结果表明，Runx 2中编码基质降解酶的基因的表达显著降低
Agc1CreER
KO小鼠。因此，我们的研究结果表明，软骨细胞中Runx 2的抑制至少可以部分挽救DMM诱导的成年小鼠OA样缺陷。
Runx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery at 12-week-old mice to induce OA in adult Runx2
Agc1CreER
mice, in which Runx2 was specifically deleted in Aggrecan-expressing chondrocytes by administering tamoxifen at 8-weeks of age. Knee joint samples were collected 8- and 12-weeks post-surgery and analyzed through histology, histomorphometry and micro-computed tomography (μCT). Our results showed that severe OA-like defects were observed after DMM surgery in Cre-negative control mice, including articular cartilage degradation and subchondral sclerosis, while the defects were significantly ameliorated in Runx2
Agc1CreER
KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2
Agc1CreER
KO mice compared to that in Cre-negative control mice. Results of quantitative reverse-transcription PCR (qRT-PCR) demonstrated that expression of the genes encoding for matrix degradation enzymes was significantly decreased in Runx2
Agc1CreER
KO mice. Thus, our findings suggest that inhibition of Runx2 in chondrocytes could at least partially rescue DMM-induced OA-like defects in adult mice.