Osteocyte-Intrinsic MMP13 exacerbates injury-induced temporomandibular joint osteoarthritis.

Abstract

OBJECTIVE: Cartilage in the knee and temporomandibular joint (TMJ) rely on subchondral bone for joint homeostasis, whereby osteoarthritis (OA) causes degeneration. In the knee, suppression of osteocytic perilacunocanalicular remodeling drives cartilage degeneration in a destabilization of the medial meniscus model of OA. Given the structural and functional differences between knee and TMJ osteochondral tissues, whether osteocytes also play a causal role in TMJOA remains to be determined. We hypothesize that subchondral bone osteocytes are required for TMJ homeostasis. METHOD: We evaluated the role of osteocytic MMP13 in the TMJ using 16-week-old mixed FVB and C57BL/6 male mice with osteocyte-intrinsic loss of MMP13 (DMP1-cre;MMP13). DMP1-cre;MMP13or Cre-negative (Control) mice received intraarticular saline or monosodium iodoacetate (MIA) to induce injury. Effects of MMP13-dependent osteocyte dysfunction on TMJ or knee OA were determined by histology and microCT. RESULTS: Unlike baseline differences in knees of DMP1-cre;MMP13and Controls, osteocytic MMP13-deficiency had no discernible effects on TMJ cartilage and subchondral bone in the absence of injury. Relative to saline Control, MIA Control mice had cartilage degeneration, with higher modified TMJ Mankin scores (p<0.001; 95%CI [-7.7 to -1.9]). MIA-injured Controls also had increased osteocyte lacunar number (p=0.03; 95% CI [-394.2 to -14.8]) and a genotype and treatment interaction effect on TRAP stain (p=0.0213;36.04% of total variation). Contrary to our hypothesis, TMJs of MIA-injured DMP1-cre;MMP13mice were protected from cartilage degeneration or subchondral bone changes. Relative to Cre-negative Controls, DMP1-cre;MMP13knees showed resistance to injury-induced increase in subchondral bone plate thickness. CONCLUSION: Despite different roles for osteocytic MMP13 in TMJ and knee, osteocytic MMP13 deficiency protects both joints from injury-dependent effects on subchondral bone.