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Polymorphisms of the <jats:italic>CALCA<\/jats:italic> gene, giving rise to either a procalcitonin\/calcitonin (<jats:italic>PCT\/CT<\/jats:italic>) or a calcitonin gene-related peptide alpha (<jats:italic>\u03b1CGRP<\/jats:italic>) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both <jats:italic>PCT\/CT<\/jats:italic> and <jats:italic>\u03b1CGRP<\/jats:italic> transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, <jats:italic>\u03b1CGRP<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and <jats:italic>CALCA<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both <jats:italic>PCT\/CT<\/jats:italic> and <jats:italic>\u03b1CGRP<\/jats:italic> transcripts is induced in ptOA knees. <jats:italic>CALCA<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to <jats:italic>\u03b1CGRP<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and WT mice. Osteophyte formation is reduced to the same extent in <jats:italic>CALCA<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and <jats:italic>\u03b1CGRP<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking <jats:italic>CALCA<\/jats:italic>. Our data show that expression of the <jats:italic>PCT\/CT<\/jats:italic> transcript protects from the progression of ptOA, while <jats:italic>\u03b1CGRP<\/jats:italic> promotes osteophyte formation, suggesting that <jats:italic>CALCA<\/jats:italic>-encoded peptides may represent novel targets for the treatment of ptOA.<\/jats:p>","DOI":"10.1038\/s42003-024-05889-0","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T07:02:32Z","timestamp":1708671752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-2152","authenticated-orcid":false,"given":"Shan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4039-6674","authenticated-orcid":false,"given":"Paul Richard","family":"Knapstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-0199","authenticated-orcid":false,"given":"Antonia","family":"Donat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly-Charlotte","family":"Albertsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sevecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Erdmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessika","family":"Appelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hildebrandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2924-7384","authenticated-orcid":false,"given":"Tazio","family":"Maleitzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Frosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Baranowsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-7288","authenticated-orcid":false,"given":"Johannes","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"5889_CR1","doi-asserted-by":"publisher","first-page":"100587","DOI":"10.1016\/j.eclinm.2020.100587","volume":"29-30","author":"A Cui","year":"2020","unstructured":"Cui, A. et al. 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