Synovial microenvironment in temporomandibular joint osteoarthritis: crosstalk with chondrocytes and potential therapeutic targets.

Temporomandibular joint osteoarthritis (TMJOA) is considered to be a low-grade inflammatory disease involving multiple joint tissues. The crosstalk between synovium and cartilage plays an important role in TMJOA. Synovial cells are a group of heterogeneous cells and synovial microenvironment is mainly composed of synovial fibroblasts (SF) and synovial macrophages. In TMJOA, SF and synovial macrophages release a large number of inflammatory cytokines and extracellular vesicles and promote cartilage destruction. Cartilage wear particles stimulate SF proliferation and macrophages activation and exacerbate synovitis. In TMJOA, chondrocytes and synovial cells exhibit increased glycolytic activity and lactate secretion, leading to impaired chondrocyte matrix synthesis. Additionally, the synovium contains mesenchymal stem cells, which are the seed cells for cartilage repair in TMJOA. Co-culture of chondrocytes and synovial mesenchymal stem cells enhances the chondrogenic differentiation of stem cells. This review discusses the pathological changes of synovium in TMJOA, the means of crosstalk between synovium and cartilage, and their influence on each other. Based on the crosstalk between synovium and cartilage in TMJOA, we illustrate the treatment strategies for improving synovial microenvironment, including reducing cell adhesion, utilizing extracellular vesicles to deliver biomolecules, regulating cellular metabolism and targeting inflammatory cytokines.

The role of YAP/TAZ on joint and arthritis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common forms of arthritis with undefined etiology and pathogenesis. Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ), which act as sensors for cellular mechanical and inflammatory cues, have been identified as crucial players in the regulation of joint homeostasis. Current studies also reveal a significant association between YAP/TAZ and the pathogenesis of OA and RA. The objective of this review is to elucidate the impact of YAP/TAZ on different joint tissues and to provide inspiration for further studying the potential therapeutic implications of YAP/TAZ on arthritis. Databases, such as PubMed, Cochran Library, and Embase, were searched for all available studies during the past two decades, with keywords "YAP," "TAZ," "OA," and "RA."

The role of neuropilin in bone/cartilage diseases.

Bone remodeling is the balance between osteoblasts and osteoclasts. Bone diseases such as osteoporosis and osteoarthritis are associated with imbalanced bone remodeling. Skeletal injury leads to limited motor function and pain. Neurophilin was initially identified in axons, and its various ligands and roles in bone remodeling, angiogenesis, neuropathic pain and immune regulation were later discovered. Neurophilin promotes osteoblast mineralization and inhibits osteoclast differentiation and its function. Neuropolin-1 provides channels for immune cell chemotaxis and cytokine diffusion and leads to pain. Neuropolin-1 regulates the proportion of T helper type 17 (Th17) and regulatory T cells (Treg cells), and affects bone immunity. Vascular endothelial growth factors (VEGF) combine with neuropilin and promote angiogenesis. Class 3 semaphorins (Sema3a) compete with VEGF to bind neuropilin, which reduces angiogenesis and rejects sympathetic nerves. This review elaborates on the structure and general physiological functions of neuropilin and summarizes the role of neuropilin and its ligands in bone and cartilage diseases. Finally, treatment strategies and future research directions based on neuropilin are proposed.