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.
Highlights
Sci. 2021, 22, 3429. https://doi.org/Osteoarthritis (OA) is a joint disorder that affects most of the joint components, such as by causing articular cartilage degeneration, synovial inflammation, subchondral bone sclerosis, osteophyte formation and/or meniscal tear [1]
cathelicidin-related antimicrobial peptide (Cramp) Is Induced by Pro-Inflammatory Cytokines via NF-κB Pathway in Chondrocytes
To examine whether IL-1β-induced expression of Cramp is mediated by NF-κB, we treated chondrocytes with SC514, an IKKβ inhibitor [44], and observed significant suppression of
Summary
Osteoarthritis (OA) is a joint disorder that affects most of the joint components, such as by causing articular cartilage degeneration, synovial inflammation, subchondral bone sclerosis, osteophyte formation and/or meniscal tear [1]. This degenerative joint disease is caused by overuse and overload of the joints together with joint inflammation, and leads to pain and disability mainly in the aging and obese populations [2]. Chondrocytes stimulated by pro-inflammatory cytokines or ECM degradation products from OA lesions express high levels of catabolic factors such as matrix metalloproteinases (MMPs) and aggrecanases (ADAMTSs) [11,12,13], which degrade the cartilage matrix.
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