The Effect of Overexpression of Lrp5 on the Temporomandibular Joint

Abstract

Objective: 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. Design: 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. Results: Subchondral bone volume (BV) and percent bone volume (BV/TV) were significantly increased in both EXP-A and EXP-G compared with CTRL (P < 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. Conclusions: These data demonstrate that Lrp5 overexpression leads to adaptation changes in the mandibular condylar cartilage of the TMJ to prevent cartilage degradation.