Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1

• Published in: PloS one Vol. 11; no. 7; p. e0159157
• Main Authors: Ge, Xianpeng, Ritter, Susan Y., Tsang, Kelly, Shi, Ruirui, Takei, Kohtaro, Aliprantis, Antonios O.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.07.2016; Public Library of Science (PLoS)
• Subjects: Abnormalities; Animals; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - physiopathology; Arthritis, Experimental - prevention & control; Biocompatibility; Biology and Life Sciences; Bone Development - genetics; Calcium-Binding Proteins - deficiency; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - physiology; Cartilage; Cartilage diseases; Cells, Cultured; Cellular proteins; Chondrocytes; Chondrocytes - physiology; Chondrogenesis - genetics; Cytokines; Cytokines - physiology; Destabilization; Diagnosis; Female; Females; Fibroblasts; Gait; Gene Deletion; Genetic aspects; Humans; Immunohistochemistry; Inflammation; Interleukins; Knee; Laboratories; Male; Medicine and Health Sciences; Meniscus; Mice; Mice, Knockout; Osteoarthritis; Osteoarthritis, Knee - genetics; Osteoarthritis, Knee - physiopathology; Osteoarthritis, Knee - prevention & control; Patients; Physiological aspects; Proteomics; Research and Analysis Methods; Rodents; Sex Characteristics; Surgery; Synovial fluid; Synovial Fluid - physiology; Tumor necrosis factor-α; Up-Regulation; Japan; Beijing China; United States > US; Massachusetts; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159157

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.