Abstract

Tenascin-C (TNC) is a large multimodular glycoprotein of the extracellular matrix that consists of four distinct domains. Emerging evidence suggests that TNC may be involved in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the current understanding of the role of TNC in cartilage and in synovial biology, across both OA and RA. TNC is expressed in association with the development of articular cartilage; the expression decreases during maturation of chondrocytes and disappears almost completely in adult articular cartilage. TNC expression is increased in diseased cartilage, synovium, and synovial fluid in OA and RA. In addition, elevated circulating TNC levels have been detected in the blood of RA patients. Thus, TNC could be used as a novel biochemical marker for OA and RA, although it has no specificity as a biochemical marker for these joint disorders. In a post-traumatic OA model of aged joints, TNC deficiency was shown to enhance cartilage degeneration. Treatment with TNC domains results in different, domain-specific effects, which are also dose-dependent. For instance, some TNC fragments including the fibrinogen-like globe domain might function as endogenous inducers of synovitis and cartilage matrix degradation through binding with toll-like receptor-4, while full-length TNC promotes cartilage repair and prevents the development of OA without exacerbating synovitis. The TNC peptide TNIIIA2 also prevents cartilage degeneration without causing synovial inflammation. The clinical significance of TNC effects on cartilage and synovium is unclear and understanding the clinical significance of TNC is not straightforward.

Highlights

  • Osteoarthritis (OA) is a well-known cause of disability, with an estimated global prevalence of more than 30% [1]

  • We present the current understanding of the role of TNC in cartilage and in synovial biology, across both OA and Rheumatoid arthritis (RA)

  • The synovium can produce soluble inflammatory mediators, including cytokines and chemokines, that are detected in joint tissues and synovial fluid in OA, and contribute to cartilage degeneration [40]

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Summary

INTRODUCTION

Osteoarthritis (OA) is a well-known cause of disability, with an estimated global prevalence of more than 30% [1]. TNC can drive a range of processes including cell migration, attachment, proliferation, and synthesis of proteases and proinflammatory cytokines [9] Growth factors, such as TGF-b, FGF, and PDGF, can induce TNC expression. When the articular cartilage of TNC-knockout mice at a postnatal age of 8 weeks was compared to that of age-matched wild-type (WT) mice, the tangential/ transitional zone was thicker and the density of chondrocytes was lower in WT mice than in the TNC-knockout mice. This observation in mice implies that TNC plays a role in increasing articular cartilage volume as well as producing ECM from birth to 2 months of age [25]

CARTILAGE REPAIR
No enhancement of synovitis
RHEUMATOID ARTHRITIS
Findings
CONCLUSION
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