Abstract
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by cartilage degeneration, disrupted subchondral bone remodeling, and synovitis, seriously affecting the quality of life of patients with chronic pain and functional disabilities. Current treatments for TMJOA are mainly symptomatic therapies without reliable long-term efficacy, due to the limited self-renewal capability of the condyle and the poorly elucidated pathogenesis of TMJOA. Recently, there has been increased interest in cellular therapies for osteoarthritis and TMJ regeneration. Mesenchymal stem cells (MSCs), self-renewing and multipotent progenitor cells, play a promising role in TMJOA treatment. Derived from a variety of tissues, MSCs exert therapeutic effects through diverse mechanisms, including chondrogenic differentiation; fibrocartilage regeneration; and trophic, immunomodulatory, and anti-inflammatory effects. Here, we provide an overview of the therapeutic roles of various tissue-specific MSCs in osteoarthritic TMJ or TMJ regenerative tissue engineering, with an additional focus on joint-resident stem cells and other cellular therapies, such as exosomes and adipose-derived stromal vascular fraction (SVF). Additionally, we summarized the updated pathogenesis of TMJOA to provide a better understanding of the pathological mechanisms of cellular therapies. Although limitations exist, MSC-centered therapies still provide novel, innovative approaches for TMJOA treatment.
Highlights
The temporomandibular joint (TMJ) is a synovial articulation that connects the mandibular condyle to the glenoid fossa of the temporal bone, and its inner space is divided into two compartments by a fibrocartilaginous TMJ disc [1]
Studies have revealed that accelerated terminal differentiation in chondrocytes, which leads to cartilage degeneration, is one of the typical characteristics in Temporomandibular joint osteoarthritis (TMJOA) animal models, and the underlying molecular mechanism is related to Indian hedgehog (Ihh), parathyroid hormone receptor 1 (PTH1R) signaling, and calcium-sensing receptor (CaSR), induced by aberrant biomechanical stress [54,55,56]
The authors further conducted a similar in vivo study using Adipose Stem Cells (ASCs) cultured in PLA discs in TMJs of rabbits. These results proved that the use of ASCs, especially predifferentiated with transforming growth factor- (TGF-)β1 in TMJ engineering, promoted fibrocartilaginous TMJ disclike tissue formation [104]
Summary
The temporomandibular joint (TMJ) is a synovial articulation that connects the mandibular condyle to the glenoid fossa of the temporal bone, and its inner space is divided into two compartments by a fibrocartilaginous TMJ disc [1] It has been considered as a bilateral diarthrodial joint according to its hinging and sliding movements and participation in essential life-support functions, such as chewing, swallowing, and speaking [2]. Apart from a brief introduction about the unique construction and molecular composition of TMJ, we will discuss the latest research progress on the pathogenesis of TMJOA and summarize the diverse categories of stem cells and their pathological mechanism in TMJOA treatment, combined with other regenerative medicine, including exosomes, “minimally manipulated MSCs,” and platelet-rich plasma. Since MSC-centered cellular therapies are still in its infancy, we will point out the limitations and controversies surrounding stem cell treatments, to provide an up-to-date review from a more objective perspective
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