Temporomandibular Joint Hypofunction Secondary to Unilateral Partial Discectomy Attenuates Degeneration in Murine Mandibular Condylar Cartilage

Abstract

Mechanical overloading of the temporomandibular joint (TMJ) promotes both the initiation and progression of TMJ osteoarthritis (OA). New preclinical animal models are needed for the evaluation of the molecular basis of cellular load transmission. This would allow a better understanding of the underlying mechanisms of TMJ-OA pain and disability, and help identify new therapeutics for its early diagnosis and management. The purpose of this study was to evaluate the role of mechanical loading in the progression of TMJ-OA in surgical instability arising from unilateral partial discectomy (UPD) in a murine model. In the theoretical modelling employed, lower joint reaction forces were observed on the chewing (working) side of the TMJ in the murine craniomandibular musculoskeletal system. Hypofunction was induced secondary to UPD through surgically manipulating the working side using an unopposed molar model. When the working side was restricted to the same side as that on which UPD was performed, late-stage degeneration of the cartilage showed a significant reduction (p<0.05), with diminished fibrillation and erosion of the articular cartilage, cell clustering, and hypocellularity. Condylar remodelling and proteolysis of proteoglycans were less affected. Thus, select and specific late-stage changes in TMJ-OA were contextually linked with the local mechanical environment of the joint. These data underscore the value of the UPD mouse model in studying mechanobiological pathways activated during TMJ-OA, and suggest that therapeutically targeting mechanobiological stimuli is an effective strategy in improving long-term biological, clinical, and patient-based outcomes.

Osteoarthritis of the Temporomandibular Joint: A Narrative Overview

“…Various animal models exist for the study of TMJOA using surgical (such as discectomy), mechanical (such as unilateral anterior cross-bite), chemical (such as intra-articular injections of monosodium iodoacetate or complete Freund’s adjuvant), and genetic techniques (such as Cre-recombination and knockout) [ 5 , 8 , 13 , 41 , 43 , 44 , 51 ]. The most commonly used techniques were discectomy [ 11 , 43 , 45 , 53 ], unilateral anterior cross-bite [ 36 , 38 , 44 , 46 , 54 , 57 ], intra-articular injections of monosodium iodoacetate [ 26 , 37 ], complete Freund’s adjuvant [ 41 , 48 ], and genetic techniques [ 8 , 49 , 51 ]. However, no gold standard animal model exists [ 42 ].…”

“…Most studies included in this literature review used animal models [5,6,8,11,13,36,38,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]57]. The most commonly investigated animals were mice and rats [5,8,11,13,36,38,[41][42][43][44][45][46][47][48][49][51][52][53][54]57]. One study was performed on rabbits [6].…”

“…OA can result in cortical bone erosion, flattening of joint compartments, osteophyte formation, subchondral sclerosis, and subcortical cyst formation [ 2 , 5 , 10 ]. Temporomandibular joint osteoarthritis (TMJOA) can lead to chronic pain and joint dysfunction including limited joint mobility and crepitus [ 5 , 7 , 11 ].…”

NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis

“…TMJ OA was induced by unilateral partial discectomy according to the methods in Xu et al ( 16 ) and our previous publications ( 5 , 15 , 20 , 52 ). In short, skeletally mature 16-week-old male and female mice from an NG2/CSPG4 knockout and control (c57 BL/6J) background were anesthetized with ketamine (100 mg/kg, Henry Schein, Dublin, Ohio) and xylazine (5 mg/kg, Akorn, Lake Forest, IL).…”

“…For histomorphometric grading of cartilage degeneration, tissue samples were fixed in 4% PFA overnight, decalcified with 4.5% EDTA for 28 days, paraffin embedded, and sectioned at 8 μm. Sections were stained using safranin-o/fast green and cartilage degeneration was staged using a Modified Mankin score according to published methods ( 15 , 16 , 20 , 52 ). For immunohistochemistry, sections were deparaffinized, treated with 132.2 mM sodium borohydride, permeabilized with methanol and 0.5% Triton (v/v), blocked in 5% donkey serum (D9663, Sigma, St. Louis, MO) for 2 h, and incubated with primary antibodies against NG2/CSPG4 (1 : 200, AB5320, Sigma-Millipore, Santa Cruz, CA).…”