Matías E M Chávez, Mecham D K, Black C S, Graf J W, Steel S D, Wilhelm S K, Andersen K M, Mitchell J A, Macdonald J R, Hollis W R, Eggett D L, Reynolds P R, Kooyman D L
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Department of Statistics, Brigham Young University, Provo, UT 84602, USA.
Arch Oral Biol. 2016 Sep;69:47-62. doi: 10.1016/j.archoralbio.2016.05.007. Epub 2016 May 14.
This study has two aims: 1. Validate a non-invasive malocclusion model of mouse temporomandibular joint (TMJ) osteoarthritis (OA) that we developed and 2. Confirm role of inflammation in TMJ OA by comparing the disease in the presence and absence of the receptor for advanced glycation end products (RAGE).
The malocclusion procedure was performed on eight week old mice, either wild type (WT) or without RAGE.
We observed TMJ OA at two weeks post-misalignment/malocclusion. The modified Mankin score used for the semi-quantitative assessment of OA showed an overall significantly higher score in mice with malocclusion compared to control mice at all times points (2, 4, 6 and 8 weeks). Mice with malocclusion showed a decrease in body weight by the first week after misalignment but returned to normal weight for their ages during the following weeks. The RAGE knock out (KO) mice had statistically lower modified Mankin scores compared to WT mice of the same age. The RAGE KO mice had statistically lower levels of Mmp-13 and HtrA1 but higher Tgf-β1, as measured by immunohistochemistry, compared to WT mice at eight weeks post malocclusion.
We demonstrate an inexpensive, efficient, highly reproducible and non-invasive model of mouse TMJ OA. The mechanical nature of the malocclusion resembles the natural development of TMJ OA in humans, making this an ideal model in future studies that aim to elucidate the pathogenesis of the disease leading to the discovery of a treatment. The RAGE plays a role in mouse TMJ OA.
本研究有两个目的：1. 验证我们开发的小鼠颞下颌关节（TMJ）骨关节炎（OA）的非侵入性错牙合模型；2. 通过比较存在和不存在晚期糖基化终产物受体（RAGE）时的疾病情况，确认炎症在TMJ OA中的作用。
对8周龄的野生型（WT）或无RAGE的小鼠进行错牙合手术。
在错牙合/咬合不正后两周，我们观察到TMJ OA。用于OA半定量评估的改良曼金评分显示，在所有时间点（2、4、6和8周），咬合不正的小鼠的总体评分显著高于对照小鼠。咬合不正的小鼠在错牙合后的第一周体重下降，但在接下来的几周内恢复到其年龄对应的正常体重。与同年龄的WT小鼠相比，RAGE基因敲除（KO）小鼠的改良曼金评分在统计学上更低。通过免疫组织化学测量，与咬合不正后8周的WT小鼠相比，RAGE KO小鼠的Mmp-13和HtrA1水平在统计学上更低，但Tgf-β1水平更高。
我们展示了一种廉价、高效、高度可重复且非侵入性的小鼠TMJ OA模型。错牙合的机械性质类似于人类TMJ OA的自然发展，这使其成为未来旨在阐明该疾病发病机制以发现治疗方法的研究中的理想模型。RAGE在小鼠TMJ OA中起作用。
