Ca-DEX Biomineralization-Inducing Nuts Reverse Oxidative Stress and Bone Loss in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease, and the inflammatory response during its development can lead to joint cartilage and bone damage up to disability. Dexamethasone (DEX) can effectively alleviate the inflammatory response in RA, but the severe adverse effects that occur after its long-term administration limit its clinical development. Herein, we propose a Ca-DEX biomineralization-inducing nut (CaCO3-DEX) with controlled release properties for mitigating the toxic side effects of DEX in RA treatment, especially the damage to cartilage and bone. CaCO3-DEX releases the drug and Ca2+ preferentially in an inflammatory environment. Both in vitro and in vivo studies demonstrate that CaCO3-DEX significantly reduces the secretion of pro-inflammatory factors and inhibits ROS production in vitro, as well as demonstrates superior pro-biomineralization and osteogenic differentiation potential. In the collagen-induced rheumatoid arthritis model (CIA model), CaCO3-DEX significantly reduces the clinical score of arthritis in mice, and the imaging results show a noticeable relief of edema and bone erosion in CIA model mice treated with CaCO3-DEX, while inflammatory factors at the injury areas are significantly reduced, which provides favorable protection to cartilage and bone.