{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:51:48Z","timestamp":1785412308714,"version":"3.56.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Cartilage, as the majority of adult mammalian tissues, has limited regeneration capacity. Cartilage degradation consecutive to joint injury or aging then leads to irreversible joint damage and diseases. In contrast, several vertebrate species such as the zebrafish have the remarkable capacity to spontaneously regenerate skeletal structures after severe injuries. The objective of our study was to test the regenerative capacity of Meckel\u2019s cartilage (MC) upon mechanical injury in zebrafish and to identify the mechanisms underlying this process.<\/jats:p><jats:p><jats:bold>Methods and Results:<\/jats:bold> Cartilage regenerative capacity in zebrafish larvae was investigated after mechanical injuries of the lower jaw MC in <jats:italic>TgBAC(col2a1a:mCherry)<\/jats:italic>, to visualize the loss and recovery of cartilage. Confocal analysis revealed the formation of new chondrocytes and complete regeneration of MC at 14\u00a0days post-injury (dpi) via chondrocyte cell cycle re-entry and proliferation of pre-existing MC chondrocytes near the wound. Through expression analyses, we showed an increase of <jats:italic>nrg1<\/jats:italic> expression in the regenerating lower jaw, which also expresses Nrg1 receptors, ErbB3 and ErbB2. Pharmacological inhibition of the ErbB pathway and specific knockdown of Nrg1 affected MC regeneration indicating the pivotal role of this pathway for cartilage regeneration. Finally, addition of exogenous NRG1 in an <jats:italic>in vitro<\/jats:italic> model of osteoarthritic (OA)-like chondrocytes induced by IL1\u03b2 suggests that Nrg1\/ErbB pathway is functional in mammalian chondrocytes and alleviates the increased expression of catabolic markers characteristic of OA-like chondrocytes.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our results show that the Nrg1\/ErbB pathway is required for spontaneous cartilage regeneration in zebrafish and is of interest to design new therapeutic approaches to promote cartilage regeneration in mammals.<\/jats:p>","DOI":"10.3389\/fcell.2023.1123299","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T04:34:44Z","timestamp":1683174884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Cartilage regeneration in zebrafish depends on Nrg1\/ErbB signaling pathway"],"prefix":"10.3389","volume":"11","author":[{"given":"Dora","family":"Sap\u00e8de","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bahraoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Abou Nassif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Barthelaix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Jorgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Djouad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6502","DOI":"10.1073\/pnas.0401711101","article-title":"Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa","volume":"101","author":"Akiyama","year":"2004","journal-title":"Proc. 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