{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:05:57Z","timestamp":1779318357312,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periodontal disease, a chronic inflammatory disorder, is increasingly linked to systemic conditions. This study investigates its causal role in muscle wasting via chronic inflammation, aiming to inform integrative therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mendelian randomization (MR) analysis was applied to assess causality. Periodontal disease-related genes were obtained from the GEO dataset GSE223924, and muscle atrophy-related targets from GeneCards. Shared targets were analyzed via protein-protein interaction (PPI) networks, followed by functional enrichment (GO\/KEGG) and immune infiltration analyses. Key molecular alterations were validated in clinical samples using qRT-PCR and Western blot. Potential therapeutics were identified through drug prediction and molecular docking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Periodontal disease promotes muscle atrophy through systemic inflammatory dysregulation. We identified 415 shared targets, with IL-6, IL-1\u03b2, and IL-10 emerging as core genes. These were enriched in the PI3K-Akt signaling pathway and correlated significantly with altered immune cell infiltration. Experimental validation confirmed dysregulation of these cytokines in patient tissues. Through drug prediction and molecular docking, exploratory potential candidate compounds were obtained. These are only the results of the preliminary virtual screening, including rofecoxib, TT-301 and nelfinavir.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study initially explored the potential positive causal relationship between periodontal disease and muscle atrophy. This relationship is mediated by chronic inflammation centered on IL-6, IL-1\u03b2, and IL-10 within the PI3K-Akt pathway. The findings provide a translational foundation for dual-targeting therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1810047","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:10:37Z","timestamp":1779315037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal association and molecular mechanisms of periodontal disease and muscle wasting and atrophy: Mendelian randomization and bioinformatics analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaxuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Stomatology, The Second Hospital of Shijiazhuang","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The Second Hospital of Shijiazhuang","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The Second Hospital of Shijiazhuang","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1111\/prd.12629","article-title":"Serum cytokines in periodontal diseases","volume":"98","author":"Ahmad","year":"2000","journal-title":"Periodontology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"960","DOI":"10.3390\/cells13110960","article-title":"Combined insults of a MASH diet and alcohol binges activate intercellular communication and neutrophil recruitment via the NLRP3-IL-1\u03b2 axis in the liver","volume":"13","author":"Babuta","year":"2024","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13411","article-title":"A principled framework for mendelian randomization in oral health research","author":"Bashir","year":"2025","journal-title":"J. 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