Metallothionein-1 is associated with osteoarthritis disease activity and suppresses proinflammatory cytokines production in synovial cells

Backgrounds: OA (Osteoarthritis) is a predominant degenerative disease, characterized by the synovial inflammation and cartilage destruction. The pathogenic mechanisms remain mostly unknown. There is an critical require for extra investigations to discover new therapeutic targets to prevent and treat OA disease, as there are currently no effective treatments except for the joint replacement. Methods: The mRNA and protein levels of Metallothionein-1(MT-1) were quantified by qPCR and ELISA in peripheral blood mononuclear cells (PBMCs), serum and synovial cells (SCs) from erosive inflammatory OA (EIOA) and primary generalized OA (PGOA) patients. Age and sex matched healthy volunteers were recruited as healthy controls (HCs). The correlation between the MT-1 level and OA activity was assessed and the anti-inflammatory effects of MT-1 was determined in vitro. Results: The mRNA and protein levels of MT-1 were significantly increased in the PBMCs and serum of EIOA patients compared with those of PGOA patients and HCs. Serum levels of MT-1 were positively correlated with VAS score, CRP, and ESR in OA patients. And the positive correlations were also identified between the MT-1 and IL-beta, TNF-alpha or IL-6 in synovial cells. Furthermore, the recombinant MT-1 protein could significantly inhibit the expression of IL-1 beta, TNF-alpha and IL-6 in PBMCs and SCs from EIOA patients in vitro. Conclusion: The data had shown that the MT-1 was up-regulated in EIOA patients and positively correlated with the disease activity. The recombinant MT-1 could suppress the expression of pro-inflammatory cytokines in both PBMCs and synovial cells from EIOA patients. Therefore, the MT-1 might become a novel therapeutic target for OA treatment.