Section of Orthodontics, Department of Growth, Development and Structure, Southern Illinois University School of Dental Medicine, Alton, IL, USA.
Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, IN, USA.
Cartilage. 2021 Dec;13(2_suppl):419S-426S. doi: 10.1177/1947603520968875. Epub 2020 Oct 30.
The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway. Increased expression of low-density lipoprotein receptor-related protein 5 (Lrp5), a co-receptor of the Wnt pathway, is associated with a high bone mass (HBM) phenotype. The objective of this study was to analyze the effect of overexpression of Lrp5 on the subchondral bone and cartilage of the TMJ in mice exhibiting the HBM phenotype.
Sixteen-week-old Lrp5 knock-in transgenic mice carrying either the A214V (EXP-A) or G171V (EXP-G) missense mutations, and wildtype controls (CTRL) were included in this study. Fluorescent bone labels, calcein, alizarin complexone, and demeclocycline were injected at 3.5, 7.5, and 11.5 weeks of age, respectively. The left mandibular condyle was used to compare the subchondral bone micro-computed tomography parameters and the right TMJ was used for histological analyses. Cartilage thickness, matrix proteoglycan accumulation, and immunohistochemical localization of Lrp5 and sclerostin were compared between the groups.
Subchondral bone volume (BV) and percent bone volume (BV/TV) were significantly increased in both EXP-A and EXP-G compared with CTRL ( < 0.05) whereas trabecular spacing (Tb.Sp) was decreased. Cartilage thickness, extracellular matrix production, and expression of Lrp5 and Sost were all increased in the experimental groups. The separation between the fluorescent bone labels indicated increased endochondral maturation between 3.5 and 7.5 weeks.
These data demonstrate that Lrp5 overexpression leads to adaptation changes in the mandibular condylar cartilage of the TMJ to prevent cartilage degradation.
颞下颌关节（TMJ）是一种独特的纤维软骨关节，通过细胞信号通路（如 Wnt 通路）适应机械负荷。低密度脂蛋白受体相关蛋白 5（Lrp5）的表达增加，Wnt 通路的一个共受体，与高骨量（HBM）表型有关。本研究的目的是分析 Lrp5 过表达对表现出 HBM 表型的小鼠 TMJ 软骨下骨和软骨的影响。
本研究纳入了 16 周龄的 Lrp5 敲入转基因小鼠，携带 A214V（EXP-A）或 G171V（EXP-G）错义突变，以及野生型对照（CTRL）。在 3.5、7.5 和 11.5 周龄时分别注射荧光骨标记物、钙黄绿素、茜素红复合物和地美环素。比较左侧下颌骨髁突的软骨下骨微计算机断层扫描参数，右侧 TMJ 用于组织学分析。比较各组间软骨厚度、基质蛋白聚糖积累以及 Lrp5 和 Sost 的免疫组织化学定位。
与 CTRL 相比，EXP-A 和 EXP-G 的软骨下骨体积（BV）和骨体积百分比（BV/TV）均显著增加（<0.05），而骨小梁间距（Tb.Sp）降低。实验组的软骨厚度、细胞外基质产生以及 Lrp5 和 Sost 的表达均增加。3.5 至 7.5 周之间荧光骨标记物之间的分离表明软骨内成熟增加。
这些数据表明，Lrp5 过表达导致 TMJ 下颌髁突软骨的适应性变化，以防止软骨降解。
