Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes
| Autor: | Anne-Christine Bay-Jensen, Morten A. Karsdal, Christian Pedersen, Sarah Juel Paulsen, Bodil-Cecilie Sondergaard, Toni Segovia-Silvestre, T. Christiansen, Suzi H Madsen |
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| Rok vydání: | 2009 |
| Předmět: |
Calcitonin
Cartilage Articular medicine.medical_specialty lcsh:Diseases of the musculoskeletal system Osteoarthritis Sulfur Radioisotopes Chondrocytes Rheumatology Downregulation and upregulation Internal medicine Oxazines Research article medicine Cyclic AMP Animals Humans Orthopedics and Sports Medicine Calcitonin receptor Receptor Collagen Type II Cells Cultured Aged biology Staining and Labeling business.industry Cartilage Middle Aged Receptors Calcitonin medicine.disease Up-Regulation medicine.anatomical_structure Endocrinology Proteoglycan Xanthenes biology.protein Female Proteoglycans Signal transduction lcsh:RC925-935 business Peptides hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | BMC Musculoskeletal Disorders BMC Musculoskeletal Disorders, Vol 11, Iss 1, p 62 (2010) |
| ISSN: | 1471-2474 |
| Popis: | Background Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA) cartilage. Methods Human OA cartilage explants were cultured with salmon calcitonin [100 pM-100 nM]. Direct effects of calcitonin on articular cartilage were evaluated by 1) measurement of proteoglycan synthesis by incorporation of radioactive labeled 35SO4 [5 μCi] 2) quantification of collagen-type-II formation by pro-peptides of collagen type II (PIINP) ELISA, 3) QPCR expression of the calcitonin receptor in OA chondrocytes using four individual primer pairs, 4) activation of the cAMP signaling pathway by EIA and, 5) investigations of metabolic activity by AlamarBlue. Results QPCR analysis and subsequent sequencing confirmed expression of the calcitonin receptor in human chondrocytes. All doses of salmon calcitonin significantly elevated cAMP levels (P < 0.01 and P < 0.001). Calcitonin significantly and concentration-dependently [100 pM-100 nM] induced proteoglycan synthesis measured by radioactive 35SO4 incorporation, with a 96% maximal induction at 10 nM (P < 0.001) corresponding to an 80% induction of 100 ng/ml IGF, (P < 0.05). In alignment with calcitonin treatments [100 pM-100 nM] resulted in 35% (P < 0.01) increased PIINP levels. Conclusion Calcitonin treatment increased proteoglycan and collagen synthesis in human OA cartilage. In addition to its well-established effect on subchondral bone, calcitonin may prove beneficial to the management of joint diseases through direct effects on chondrocytes. |
| Databáze: | OpenAIRE |
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