Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, 60612, USA.
State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
Sci Rep. 2017 May 24;7(1):2371. doi: 10.1038/s41598-017-02490-w.
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 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 KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2 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 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.
Runx2 可能在骨关节炎（OA）的发展中发挥重要作用。然而，Runx2 在关节软骨细胞功能中的具体作用以及在成年小鼠 OA 发展中的作用尚未完全确定。在这项研究中，我们在 12 周龄的小鼠中进行内侧半月板不稳定（DMM）手术，以在成年 Runx2 敲除小鼠中诱导 OA，其中在 8 周龄时用他莫昔芬特异性敲除 Aggrecan 表达的软骨细胞中的 Runx2。在手术后 8 周和 12 周收集膝关节样本，并通过组织学、组织形态计量学和微计算机断层扫描（μCT）进行分析。我们的结果表明，在 Cre 阴性对照小鼠中，DMM 手术后出现了严重的 OA 样缺陷，包括软骨降解和软骨下硬化，而在 Runx2 敲除小鼠中，这些缺陷明显得到了改善。免疫组织化学（IHC）结果显示，与 Cre 阴性对照小鼠相比，Runx2 敲除小鼠中的 MMP13 表达明显降低。定量逆转录 PCR（qRT-PCR）的结果表明，Runx2 敲除小鼠中编码基质降解酶的基因表达明显降低。因此，我们的研究结果表明，在软骨细胞中抑制 Runx2 至少可以部分挽救成年小鼠 DMM 诱导的 OA 样缺陷。
