Abstract
The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.
Highlights
Of the more than 100 different types of arthritis, rheumatoid arthritis (RA) and osteoarthritis (OA) are two of the most common [1]
The CCN family consists of six matricellular proteins, cysteine-rich 61 (CYR61/CCN1), connective tissue growth factor (CTGF/CCN2), nephroblastoma-overexpressed (NOV/CCN3), Wnt-1 induced secreted protein-1 (WISP1/CCN4), Wnt-1 induced secreted protein-2 (WISP2/CCN5) and Wnt-1 induced secreted protein-3 (WISP3/CCN6), all of which are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation [9]
It has been hypothesized that articular chondrocytes promote CCN2 production in OA cartilage, and thereby, increase the cell number and compensate for the deficiency in the extracellular matrix (ECM) [51]. This is supported by research showing that in rats with monoiodoacetic acid (MIA)-induced OA, a single injection of recombinant CCN2 into the joint cavity effectively repaired articular cartilage and ameliorated OA disease, which suggests that CCN2 may help to regenerate articular cartilage [52]
Summary
Of the more than 100 different types of arthritis, rheumatoid arthritis (RA) and osteoarthritis (OA) are two of the most common [1]. OA is a whole-joint disease involving the increased remodeling of the articular cartilage, subchondral bone and bone marrow compartments, as well as the synovium, during its onset and progression [3] These are two distinct arthritis diseases, some similar clinical and pathological manifestations exist, such as joint stiffness, synovial inflammation, destruction of the articular cartilage and bone erosion [4]. The CCN family consists of six matricellular proteins, cysteine-rich 61 (CYR61/CCN1), connective tissue growth factor (CTGF/CCN2), nephroblastoma-overexpressed (NOV/CCN3), Wnt-1 induced secreted protein-1 (WISP1/CCN4), Wnt-1 induced secreted protein-2 (WISP2/CCN5) and Wnt-1 induced secreted protein-3 (WISP3/CCN6), all of which are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation [9] They are well recognized for their important roles in many cellular processes including cell proliferation, adhesion, migration and differentiation, and the regulation of extracellular matrix (ECM) differentiation [9]. This review discusses the evidence regarding the involvement of CCN proteins in RA and OA (see Table 1 and Figure 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
