Molecular signaling in temporomandibular joint osteoarthritis

Abstract

Objective: Temporomandibular joint (TMJ) osteoarthritis (OA) is a type of TMJ disorders with clinical symptoms of pain, movement limitation, cartilage degeneration and joint dysfunction. This review article is aiming to summarize recent findings on signaling pathways involved in TMJ OA development and progression.

Methods: Most recent findings in TMJ OA studies have been reviewed and cited.

Results: TMJ OA is caused by inflammation, abnormal mechanical loading and genetic abnormalities. The molecular mechanisms related to TMJ OA have been determined using different genetic mouse models. Recent studies demonstrated that several signaling pathways are involved in TMJ OA pathology, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, which are summarized in this review article. Alterations of these signaling pathways lead to the pathological changes in TMJ tissues, affecting cartilage matrix degradation, catabolic metabolism and chondrocyte apoptosis.

Conclusion: Multiple signaling pathways were involved in the pathological process of TMJ OA. New therapeutic strategies, such as stem cell application, gene editing and other techniques may be utilized for TMJ OA treatment.

The translational potential of this article: TMJ OA is a most important subtype of TMJ disorders and may lead to substantial joint pain, dysfunction, dental malocclusion, and reduced health-related quality of life. This review article summarized current findings of signaling pathways involved in TMJ OA, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, to better understand the pathological mechanisms of TMJ OA and define the molecular targets for TMJ OA treatment.

Keywords: Cartilage degradation; Mechanical loading; Molecular signaling; Osteoarthritis; Temporomandibular joint.

Figure 1

Schematic diagram of multiple signaling pathways in TMJ OA chondrocytes. Alterations of Wnt/β-catenin, TGF-β, Ihh, FGF, NF-κB, and Notch signaling pathways lead to increased expression of matrix degrading proteases, including MMPs and Adamts4/5, promoting cartilage degradation. The activation of Wnt/β-catenin signaling also affect subchondral bone of TMJ. The activation of Ihh pathway affects chondrocyte differentiation and maturation through PTHrP. The activation of NF-κB, and Notch pathways induces inflammation and accelerates TMJ OA development.