title: 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.
abstract: Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.
authors: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.|Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, College of Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors: Barbara D
authors: BD
authors: Boyan
authors: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors: Sharon L
authors: SL
authors: Hyzy
authors: School of Mechanical Engineering, College of Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors: Qingfen
authors: Q
authors: Pan
authors: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors: Kayla M
authors: KM
authors: Scott
authors: Department of Orthopedic Surgery, University of California San Diego, San Diego, California, United States of America.
authors: Richard D
authors: RD
authors: Coutts
authors: Department of Orthopedic Surgery, University of California San Diego, San Diego, California, United States of America.
authors: Robert
authors: R
authors: Healey
authors: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.|Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors: Zvi
authors: Z
authors: Schwartz
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000009:adverse effects; D008297:Male; D020370:Osteoarthritis, Knee / Q000517:prevention & control*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014815:Vitamins; D015650:24,25-Dihydroxyvitamin D 3