Abstract
Cartilage acidic protein 1 (CRTAC1) was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA) by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM) surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA.
Highlights
Osteoarthritis (OA) is the most common joint disease and a major cause of disability and rising health care costs [1, 2]
We identify cartilage acidic protein 1 (CRTAC1) as a novel regulator of OA pathogenesis
CRTAC1 is induced by pro-inflammatory cytokines in articular chondrocytes and synovial fibroblasts and deletion of this gene in female mice inhibits the development of OA
Summary
Osteoarthritis (OA) is the most common joint disease and a major cause of disability and rising health care costs [1, 2]. Epidemiologic studies show that sex-differences exist in the incidence and severity of OA, and women have higher risks and tend to develop more severe OA [3,4,5]. Great efforts have been made to understand the pathophysiology of OA and to PLOS ONE | DOI:10.1371/journal.pone.0159157. CRTAC1 in Osteoarthritis develop therapeutics, current medications only target symptoms. There are no treatments available to prevent or block the progression of structural deterioration of the joint [6]. A better understanding of the biologic processes that drive OA, and in particular sex-specific mechanisms, could lead to new targets, and eventually disease modifying therapy
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