Temporomandibular joint disorders (TMJDs) are a highly prevalent spectrum of conditions occurring in about 6 to 12% of the adult US population totaling over 10 million people and costing billions of dollars in health care and lost productivity. TMJDs frequently present with pain, functional limitations and joint sounds associated with degenerative joint disease, an osteoarthritis (OA)-like condition that significantly affects the quality of life due to its impact on critical functions such as eating and speech. While the etiologies of the temporomandibular joint (TMJ) OA remain unknown, due to the propensity of these disorders in adolescent females- an age group that coincides with orthodontic treatment- orthodontic therapy has often been attributed as a causative or predisposing factor for TMJ OA. Furthermore, severe forms of these disorders such as idiopathic condylar resorption impact on the orthodontist’s ability to deliver predictable treatment outcomes. Thus, understanding the causation or predisposing factors for TMJ OA are of critical importance to our profession.
The loss of cartilage extracellular matrix and a compromised subchondral bone are characteristic features of OA of the TMJ. While previous concepts of OA pathogenesis have proposed that cartilage loss is a primary contributor or initiator of OA, more recently it has become clear that cartilage-bone cross-talk are key elements in the pathogenesis of OA. Thus, altered bone quality including its increased or decreased density are known to lead to cartilaginous defects and progression of OA. Bone quality in turn is determined by bone forming and degrading cells including osteoblasts, osteocytes and osteoclasts. Although osteocytes have come to be recognized as key regulators of bone quality, their role in contributing to OA is not currently known. Published data has shown that osteocyte-mediated remodeling is essential for bone and joint health in long bones. More specifically, we have shown that mice with osteocyte specific ablation of matrix metalloproteinase-13 (MMP13), which is involved in perilacunar remodeling (PLR) by osteocytes have bone quality defects due to collagen disorganization and matrix hypermineralization. However, the role of osteocyte function and osteocyte-mediated bone remodeling in TMJ OA remains unknown. Because OA is a disorder that involves complex and as yet largely unknown cross-talk between cartilage and subchondral bone, we anticipate a potential link between altered bone metabolism through loss of MMP-13 in osteocytes and TMJ OA. Our long-term goal is to understand the contribution of osteocyte-mediated bone phenotypic changes to the progression and severity of TMJ OA by testing the hypothesis that altered PLR through osteocyte-specific knockdown of MMP13 aggravates chemically-induced TMJ OA. Towards this long-term goal, here we performed studies to address the following Specific Aims:
1. Establish and confirm a reproducible and effective method for intra-articular injection of OA-inducing agent, monosodium iodoacetate (MIA) by administration of Fast Green dye.
2. Using data from previous studies on mouse knee joint and rat TMJ, test and establish an effective dose of an OA-inducing agent, monosodium iodoacetate (MIA) that results in OA-like changes in the mouse TMJ.
3. Histologically quantify TMJ health via modified Mankin scoring in WT and MMP13OCY-/- male mice.
Besides providing fundamental information on osteochondral interactions and the role of each of these tissues to the initiation and / or progression of TMJ OA, this study will be important in better understanding the pathogenesis of this disorder and in providing insights into potential therapeutic targets to prevent or alleviate degenerative diseases of the TMJ. Furthermore, determination of an effective MIA dose that generates TMJ OA will establish a mice model for TMJ OA that could be valuable for future studies to identify disease mechanisms.
