title: Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.
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.
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.|Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xianpeng
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Ritter
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Tsang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.|Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Shi
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama, Japan.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Takei
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Antonios O
authors.initials: AO
authors.lastname: Aliprantis
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D001846:Bone Development / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology; D020219:Chondrogenesis / Q000235:genetics; D016207:Cytokines / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D012727:Sex Characteristics; D013582:Synovial Fluid / Q000502:physiology; D015854:Up-Regulation
chemical_list: C422245:CRTAC1 protein, human; D002135:Calcium-Binding Proteins; C560339:Crtac1 protein, mouse; D016207:Cytokines