Degradative Pathways in Tissues of the Temporomandibular Joint

Abstract

Identification of a small animal model that undergoes pathological temporomandibular joint (TMJ) degeneration would represent a significant research tool. To date however, no such model has been described. We therefore have investigated the pathological and immunohistochemical features of the TMJ of a transgenic mouse that over expresses the human form of TNFα. The TMJ of this animal appears to undergo changes that resemble arthriditics of temporomandibular dysfunction. Furthermore, the disc and articular cells express MMP9 and IL-1. Future work should validate this animal model as one that would have utility for the study of TMJ disorders. Maintenance of connective tissues in joints such as the TMJ is a normal process that allows for the reconstitution of important anatomic features. This maintenance involves both the removal and re-synthesis of structural proteins such as collagens, elastins and proteoglycans. An imbalance in the pathways for degradation and synthesis can lead to the degeneration of joint tissues. We describe the presence of a matrix metalloproteinase, MMP9 (92-kD gelatinase), in TMJ disc and articular cells that likely function in the degradative process. Additionally, we show that this enzyme is under the control of pro-inflammatory cytokines whereby TGFβ and IL-1 stimulate and PGE₂ inhibits its activity.

Pathophysiological Mechanisms in Osteoarthritis Lead to Novel Therapeutic Strategies

“…The proinflammatory cytokines, IL-1 and TNF-·, have been identified as playing critical roles in initiating apoptosis and upregulating MMP gene expression in peripheral joint OA. These mediators have also been identified as playing key roles in TMJ disease [Puzas et al, 2001;Kacena et al, 2001]. An understanding of the signaling pathways that regulate the expression of tumor suppressor genes, such as p53, must also be examined in that p53 not only alters IGF-1 [Prisco et al, 1997] and IGFBP gene expression [Buckbinder et al, 1995], but MMP-13 expression as well [Sun et al, 2000a].…”

“…Three enzymes are believed to regulate the turnover of extracellular matrix proteins, namely collagenase, responsible for degradation of native collagen fibers, stromelysins which degrade proteoglycan and type IX collagen and gelatinase(s) which degrade denatured collagen [Martel-Pelletier et al, 1999a;Smith, 1999]. Of particular importance to an understanding of the pathology of OA is the notion that while many potential MMPs have the capacity to degrade cartilage matrix proteins [Puzas et al, 2001], not all appear to be particularly important in OA. Thus, it is critical to catalog and understand the regulation of those MMP genes that appear to be intimately involved in OA as distinct from MMPs that participate in extracellular matrix protein turnover, in general.…”

Subchondral Bone Resorption in Temporomandibular Joint Disorders

“…Puzas et al [2001] have recently investigated cartilage degradative mechanisms in the TMJ of a transgenic mouse model with overexpression of tumor necrosis factor alpha), but there have been few basic science investigations into bone resorption in TMD. Yasuoka et al [2000] investigated the effect of estrogen replacement on TMJ remodeling in ovariectomized rats and noted that in animal studies it is important to relate the region of study in the mandibular condyle to site-related differential growth due to feeding habits.…”

Osteoarthritis in temporomandibular joint of Col2a1 mutant mice

“…An OA animal model is an important tool in understanding TMJ disease (2, 10, 15, 18). Human studies can only describe TMJ OA, whereas animal models may elucidate a cause and effect relationship that might allow for TMJ disease reversal and a universal understanding of TMJ OA pathobiochemistry that is not currently available (14).…”