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However, the molecular events underlying these effects at the tissue\u2013implant interface have not been fully elucidated. This study aimed to determine the major molecular mediators associated with compromised osseointegration due to previous exposure to radiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Titanium implants were placed in rat tibiae with or without pre\u2010exposure to 20\u2009Gy irradiation. Histomorphometric, biomechanical, quantitative polymerase chain reaction (qPCR) and enzyme\u2010linked immunosorbent assay analyses were performed at 1 and 4\u2009weeks after implantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The detrimental effects of irradiation were characterized by reduced bone\u2013implant contact and removal torque. Furthermore, pre\u2010exposure to radiation induced different molecular dysfunctions such as (i) increased expression of pro\u2010inflammatory (<jats:italic>Tnf<\/jats:italic>) and osteoclastic (<jats:italic>Ctsk<\/jats:italic>) genes and decreased expression of the bone formation (<jats:italic>Alpl<\/jats:italic>) gene in implant\u2010adherent cells; (ii) increased expression of bone formation (<jats:italic>Alpl<\/jats:italic> and <jats:italic>Bglap<\/jats:italic>) genes in peri\u2010implant bone; and (iii) increased expression of pro\u2010inflammatory (<jats:italic>Tnf<\/jats:italic>) and pro\u2010fibrotic (<jats:italic>Tgfb1<\/jats:italic>) genes in peri\u2010implant soft tissue. The serum levels of pro\u2010inflammatory, bone formation and bone resorption proteins were greater in the irradiated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Irradiation causes the dysregulation of multiple biological activities, among which perturbed inflammation seems to play a common role in hindering osseointegration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.14021","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T06:19:55Z","timestamp":1716790795000},"page":"1236-1251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular mechanisms of poor osseointegration in irradiated bone: In vivo study in a rat tibia model"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2610-1294","authenticated-orcid":false,"given":"Omar","family":"Omar","sequence":"first","affiliation":[{"name":"Department of 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