Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes
<p>Abstract</p> <p>Background</p> <p>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 pos...
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| Format: | Article |
| Language: | English |
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BMC
2010-04-01
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| Series: | BMC Musculoskeletal Disorders |
| Online Access: | http://www.biomedcentral.com/1471-2474/11/62 |
| _version_ | 1819203727417933824 |
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| author | Pedersen Christian Christiansen Thorbjorn Paulsen Sarah J Segovia-Silvestre Toni Madsen Suzi H Sondergaard Bodil-Cecilie Bay-Jensen Anne-Christine Karsdal Morten A |
| author_facet | Pedersen Christian Christiansen Thorbjorn Paulsen Sarah J Segovia-Silvestre Toni Madsen Suzi H Sondergaard Bodil-Cecilie Bay-Jensen Anne-Christine Karsdal Morten A |
| author_sort | Pedersen Christian |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <sup>35</sup>SO<sub>4 </sub>[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.</p> <p>Results</p> <p>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 <sup>35</sup>SO<sub>4 </sub>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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-23T04:24:31Z |
| format | Article |
| id | doaj.art-25e090212fdb4fb8a5c60a1799fa788c |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-12-23T04:24:31Z |
| publishDate | 2010-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-25e090212fdb4fb8a5c60a1799fa788c2022-12-21T18:00:09ZengBMCBMC Musculoskeletal Disorders1471-24742010-04-011116210.1186/1471-2474-11-62Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytesPedersen ChristianChristiansen ThorbjornPaulsen Sarah JSegovia-Silvestre ToniMadsen Suzi HSondergaard Bodil-CecilieBay-Jensen Anne-ChristineKarsdal Morten A<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <sup>35</sup>SO<sub>4 </sub>[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.</p> <p>Results</p> <p>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 <sup>35</sup>SO<sub>4 </sub>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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2474/11/62 |
| spellingShingle | Pedersen Christian Christiansen Thorbjorn Paulsen Sarah J Segovia-Silvestre Toni Madsen Suzi H Sondergaard Bodil-Cecilie Bay-Jensen Anne-Christine Karsdal Morten A Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes BMC Musculoskeletal Disorders |
| title | Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes |
| title_full | Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes |
| title_fullStr | Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes |
| title_full_unstemmed | Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes |
| title_short | Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes |
| title_sort | investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes |
| url | http://www.biomedcentral.com/1471-2474/11/62 |
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