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The objective is to understand whether <jats:italic>Rsk2<\/jats:italic>, previously shown to have protective effects in long bones against TNF\u03b1-induced bone resorption, exhibits similar effects in the craniofacial region.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Materials<\/jats:title>\n            <jats:p>, and Methods.<\/jats:p>\n            <jats:p>The study compares mice with TNF\u03b1 overexpression, <jats:italic>Rsk2<\/jats:italic> knockout mice, and a combination of TNF\u03b1, and <jats:italic>Rsk2<\/jats:italic> knockout mice using detailed micro-computed tomography coupled with landmark based morphometric analysis, and classical histology. The overall skull morphology, mandible shape, and the temporomandibular joint were examined. Additionally, histological sections were utilized to examine the synovial membrane.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Combining TNF\u03b1, and <jats:italic>Rsk2<\/jats:italic> deficiency does not further alter overall skull shape compared to TNF\u03b1 alone. TNF\u03b1 overexpression shortens the mandibular ramus, exacerbated by <jats:italic>Rsk2<\/jats:italic> absence. Micro-computed tomography (\u00b5CT) reveals significant temporomandibular joint damage from TNF\u03b1, independent of <jats:italic>Rsk2<\/jats:italic>. However, histological sections show increased synovial membrane thickness with TNF\u03b1, heightened in the absence of <jats:italic>Rsk2<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              <jats:italic>Rsk2<\/jats:italic> mitigates TNF\u03b1-induced effects on mandibular ramus length in the craniofacial system but has limited impact on the temporomandibular joint, except for synovial membrane thickness. Overall, <jats:italic>Rsk2<\/jats:italic> demonstrates a weaker preventive effect on TNF\u03b1-induced craniofacial bone loss compared to its established role in the appendicular skeleton.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Relevance<\/jats:title>\n            <jats:p>This study highlights regional differences in <jats:italic>Rsk2's<\/jats:italic> protective mechanisms, emphasizing the need for further exploration of the underlying mechanisms for these disparities. Understanding these regional differences can be crucial for the development of targeted therapeutic interventions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12903-025-05779-9","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T08:55:14Z","timestamp":1742979314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The effect of Rsk2 on TNF\u03b1-mediated bone loss in the TMJ and craniofacial skeleton"],"prefix":"10.1186","volume":"25","author":[{"given":"Gina Marie","family":"Georgi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Bachmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Luther","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Derer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Heimel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Tangl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e4rbel","family":"Kahl-Nieke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"LeBlanc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Helms","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Amling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Schinke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till","family":"Koehne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"5779_CR1","doi-asserted-by":"publisher","unstructured":"Kim JM, Lin C, Stavre Z, Greenblatt MB, Shim JH. 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