Cyr61 participates in the pathogenesis of rheumatoid arthritis via promoting MMP-3 expression by fibroblast-like synoviocytes

Abstract

This study provides new evidence that Cyr61 participates in RA pathogenesis not only as a pro-inflammatory factor but also plays a key role in bone erosion via promoting MMP-3 expression. We suggest that targeting of Cyr61 may represent a potential strategy in RA treatment.

Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9

“…In agreement with the proposal, treatment of mice that had collagen‐induced arthritis using a murine monoclonal antibody specifically targeting CCN1, namely, 093G9, led to amelioration of the inflammation reaction and down‐regulation of Th17 population, accompanied by both decreased IL‐6 production in synovial tissues and IL‐6R expression on the surface of T cells . In addition, CCN1 participates in the pathogenesis of RA via promotion of proIL‐1β production and MMP‐3 expression by FLS, and 093G9 is effective to antagonize the effects of CCN1 …”

“…Previously, we have demonstrated that 093G9 is effective to antagonize the function of CCN1 and has great potential for the treatment of RA . In this study, we mapped the CCN1 epitope for 093G9, which is located in the IGFBP domain of CCN1.…”

“…D, Hydrophobic interactions of Phe P7 with the surrounding residues 4 | DISCUSSION Previously, we have demonstrated that 093G9 is effective to antagonize the function of CCN1 and has great potential for the treatment of RA. 7,9,11 In this study, we mapped the CCN1 epitope for 093G9, which is located in the IGFBP domain of CCN1. Consistently, it has been shown that the IGFBP domain of CCN1 is required for CCN1 to stimulate MMP1 expression.…”

“…5 It can also induce fibroblast senescence and restrict fibrosis during tissue repair. 6 Recently, with a series of studies, we demonstrated that CCN1 is involved in the pathogenesis of rheumatoid arthritis (RA) [7][8][9][10][11] ( Figure S2). CCN1 is overexpressed in synovial tissue and fibroblast-like synoviocytes (FLS) of patients with RA.…”

“…8 In addition, CCN1 participates in the pathogenesis of RA via promotion of proIL-1β production and MMP-3 expression by FLS, and 093G9 is effective to antagonize the effects of CCN1. 9,11 Besides its role in RA, CCN1 is also associated with multiple diseases including fibrosis, cardiovascular diseases, nephropathy and retinopathy, 12 and psoriasis, 11 and with multiple cancers including prostate cancer, 13 breast cancer, [14][15][16][17] and hepatocellular carcinoma. 18 CCN1 is highly expressed in psoriasis patients and imiquimod-and I-23-treated psoriasis-like mice, and 093G9 alleviates epithelial hyperplasia in psoriasis-like mice.…”