Intra-Articular Administration of Cramp into Mouse Knee Joint Exacerbates Experimental Osteoarthritis Progression

Abstract

Osteoarthritis (OA) is the most common type of arthritis and is associated with wear and tear, aging, and inflammation. Previous studies revealed that several antimicrobial peptides are up-regulated in the knee synovium of patients with OA or rheumatoid arthritis. Here, we investigated the functional effects of cathelicidin-related antimicrobial peptide (Cramp) on OA pathogenesis. We found that Cramp is highly induced by IL-1β via the NF-κB signaling pathway in mouse primary chondrocytes. Elevated Cramp was also detected in the cartilage and synovium of mice suffering from OA cartilage destruction. The treatment of chondrocytes with Cramp stimulated the expression of catabolic factors, and the knockdown of Cramp by small interfering RNA reduced chondrocyte catabolism mediated by IL-1β. Moreover, intra-articular injection of Cramp into mouse knee joints at a low dose accelerated traumatic OA progression. At high doses, Cramp affected meniscal ossification and tears, leading to cartilage degeneration. These findings demonstrate that Cramp is associated with OA pathophysiology.

Nanoparticle-Based Drug Delivery System—A Target Strategy for Osteoarthritis Treatment

“…The ideal model should include the following features: (1) all joint tissues (as the human body) are affected; (2) early stages of the disease are included; (3) animal models can simulate human disease; (4) animal species are easy to handle and raise; (5) the results can be evaluated in different biochemical, genetic, and imaging biomarkers, and should be transferable to the specificity of human medical therapeutics and pathology. It is recommended to consider the following points when selecting the OA model: the stage of OA that needs to be studied, the expansion of the lesion (focal or systemic), the therapeutic effect, and the target tissue to be studied (cartilage, membrane, bones, or synovial fluid) [90].…”

Cathelicidin‐related antimicrobial peptide mediates skeletal muscle degeneration caused by injury and Duchenne muscular dystrophy in mice

“… 10 , 11 The pleiotropic promotion or protective roles of cathelicidins have recently been elucidated in the context of tissue degeneration associated with sterile inflammation. 12 , 13 , 14 , 15 The role of cathelicidins in skeletal muscle pathology and their molecular targets have yet to be explored.…”

“…These AMPs function as potent immune modulators by killing bacteria, neutralizing bacterial lipopolysaccharide, functioning as chemoattractants for immune cells and/or activating innate immune responses 10,11 . The pleiotropic promotion or protective roles of cathelicidins have recently been elucidated in the context of tissue degeneration associated with sterile inflammation 12–15 . The role of cathelicidins in skeletal muscle pathology and their molecular targets have yet to be explored.…”

Musculoskeletal Development and Skeletal Pathophysiology’s

“…Cathelicidin-related antimicrobial peptide (Cramp) is an antimicrobial molecule produced by innate immune cells that functions to promote cell proliferation and migration. In work by Choi et al, the authors demonstrate that inflammatory mediators induce Cramp expression by chondrocytes and that Cramp stimulates chondrocyte catabolism, and accelerates OA progression in a murine model [ 6 ]. Ramesova et al demonstrate that caspase-1 helps to regulate chondrocyte differentiation and lipid metabolism, suggesting a potential role for caspase-1 in diet-induced osteoarthritis, in which increased levels of systemic inflammation are observed [ 7 ].…”