The role of TGF-beta3 in cartilage development and osteoarthritis

Abstract

Articular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, plays a versatile role in cartilage physiology and pathology. TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-β3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.

Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling

“…For instance, inhibiting TGF-β expression in synovial tissue could reduce synovial fibrosis in KOA ( Remst et al, 2014 ). However, given that TGF-β inhibits collagen deposition and is essential for preserving the homeostasis of the ECM environment, its absence will undoubtedly make it more difficult to maintain cartilage homeostasis in the knee ( Du et al, 2023 ). Thus, TGF-β is a double-edged sword.…”

Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability

“…Osteoarthritis is a typical degenerative disease that affects whole joint tissues, including the cartilage layer, subchondral bone, menisci, and peripheral synovium. [60][61][62][63][64] Previous reports have focused on the key role of chemical factors to explain the occurrence and deterioration of OA. For example, upregulation of proinflammatory factors, including interleukins (ILs), tumor necrosis factors (TNFs), leukotrienes, and pain-related prostaglandin E2 (PGE2), has showed their high expressions with the progress of OA, leading to degradation of the entire joint tissues by activating hydrolases such as matrix metalloproteinases (MMPs).…”

“…[115] Biochemical factors including TGF𝛽s and bone morphogenetic proteins (BMPs) are revealed in the terminal differentiation of matured chondrocytes and the final osteophyte formation by endochondral ossification. [62,116,117] And importantly, Lee et al showed the interaction between chemical factor signaling and mechanical sensitive mediator, piezo1, could form a pathological feed-forward network to deteriorate OA, which indicated the mechanical transduction-triggered chemical events. [118] In our current study, we only showed the chondrocyte phenotype changes in response to ECM stiffening in the cartilage tissue of osteoarthritis mouse model (Figure 7), aiming to addressing the correlation between chondrocyte phenotype and ECM stiffening.…”

“…[ 115 ] Biochemical factors including TGFβs and bone morphogenetic proteins (BMPs) are revealed in the terminal differentiation of matured chondrocytes and the final osteophyte formation by endochondral ossification. [ 62,116,117 ] And importantly, Lee et al. showed the interaction between chemical factor signaling and mechanical sensitive mediator, piezo1, could form a pathological feed‐forward network to deteriorate OA, which indicated the mechanical transduction‐triggered chemical events.…”

Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis

“…TGF‐β3 maintains the balance between chondroblast differentiation and chondrocyte hypertrophy, and its regulatory role is particularly important in chondrogenesis. Recently, TGF‐β3 has been recognized as a potential therapeutic target for OA due to its protective effect by enhancing the recruitment of autologous MSCs to damaged cartilage (Du et al, 2023). Smads regulate chondrogenesis and MSC differentiation.…”