24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats
Autor: | Qingfen Pan, Richard D. Coutts, Barbara D. Boyan, Sharon L. Hyzy, Zvi Schwartz, Kayla M. Scott, Robert M. Healey |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cartilage Articular Male Pathology Cell signaling 24 25-Dihydroxyvitamin D 3 Physiology Knees Interleukin-1beta lcsh:Medicine Osteoarthritis Knee Joints Signal transduction Pathology and Laboratory Medicine Injections Intra-Articular 0302 clinical medicine Animal Cells Synovial Fluid Medicine and Health Sciences lcsh:Science Musculoskeletal System Immune Response Cells Cultured Connective Tissue Cells Multidisciplinary Chemistry Signaling cascades Vitamins Osteoarthritis Knee Body Fluids Dose–response relationship medicine.anatomical_structure Connective Tissue Legs Anatomy Cellular Types Research Article medicine.medical_specialty Anterior cruciate ligament Immunology Chondrocyte Transforming Growth Factor beta1 03 medical and health sciences Chondrocytes Signs and Symptoms Rheumatology In vivo Diagnostic Medicine Internal medicine medicine Animals Humans 030203 arthritis & rheumatology Inflammation Dose-Response Relationship Drug Cartilage Arthritis Anterior Cruciate Ligament Injuries lcsh:R Limbs (Anatomy) Biology and Life Sciences Cell Biology Articular cartilage damage medicine.disease Rats Joints (Anatomy) Disease Models Animal 030104 developmental biology Endocrinology Biological Tissue TGF-beta signaling cascade Gene Expression Regulation Apoptosis lcsh:Q Articular Cartilage |
Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 8, p e0161782 (2016) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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