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A single 5\u2010mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (<jats:styled-content style=\"fixed-case\">CSS<\/jats:styled-content>) alone (G1); defect treated with low\u2010level laser therapy (<jats:styled-content style=\"fixed-case\">LLLT<\/jats:styled-content>) (wavelength 780\u00a0nm; total energy density 120\u00a0J\/cm<jats:sup>2<\/jats:sup>; power 50\u00a0mW) alone (G2); and <jats:styled-content style=\"fixed-case\">CSS<\/jats:styled-content> associated with <jats:styled-content style=\"fixed-case\">LLLT<\/jats:styled-content> treatment (G3). After surgery, animals in each group were euthanized at 21\u00a0days and 30\u00a0days (<jats:italic>n<\/jats:italic>\u00a0=\u00a05 per euthanasia time group). Bone formation was monitored by X\u2010ray imaging analysis. Biopsies were collected and processed for histological analysis and immunohistochemical evaluation of transforming growth factor\u2010beta (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2), fibroblast growth factor\u20102 (<jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\u20102), osteoprotegerin (<jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content>) and receptor activator of nuclear factor \u0199 (<jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>). Osteocalcin (<jats:styled-content style=\"fixed-case\">OCN<\/jats:styled-content>) was detected by immunofluorescence analysis. Compared to the G0 group, defects in the 30\u2010day G3 group exhibited increased bone formation, both by increase in radiopaque areas (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and by histomorphometric analysis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). The histopathological analysis showed a decreased number of inflammatory cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). The combined <jats:styled-content style=\"fixed-case\">CCS<\/jats:styled-content>\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">LLLT<\/jats:styled-content> (G3) treatment also resulted in the most intense immunostaining for <jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> RANK<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> FGF<\/jats:styled-content>\u20102 and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2, and the most intense and diffuse <jats:styled-content style=\"fixed-case\">OCN<\/jats:styled-content> immunofluorescent labelling at 30\u00a0days postsurgery (G3 <jats:italic>vs<\/jats:italic>. G0 group, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Therefore, the use of <jats:styled-content style=\"fixed-case\">CCS<\/jats:styled-content> associated with <jats:styled-content style=\"fixed-case\">LLLT<\/jats:styled-content> could offer a synergistic advantage in improving the healing of bone fractures.<\/jats:p>","DOI":"10.1111\/iep.12226","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T02:12:43Z","timestamp":1496110363000},"page":"75-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Low\u2010level laser therapy (780\u00a0nm) combined with collagen sponge scaffold promotes repair of rat cranial critical\u2010size defects and increases <scp>TGF<\/scp>\u2010\u03b2, <scp>FGF<\/scp>\u20102, <scp>OPG<\/scp>\/<scp>RANK<\/scp> and osteocalcin expression"],"prefix":"10.1111","volume":"98","author":[{"given":"Lana Sarita de Souza","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Department of Dentistry Post\u2010Graduation Program in Public Health Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-4695","authenticated-orcid":false,"given":"Aurigena Antunes","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology Post Graduation Program in Public Health\/Post Graduation Program in Pharmaceutical Science Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo Fernandes","family":"de Ara\u00fajo J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Morphology Post Graduation Program in Health Science\/Post Graduation Program in Functional and Structural Biology Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-9919","authenticated-orcid":false,"given":"Carlos Augusto Galv\u00e3o","family":"Barboza","sequence":"additional","affiliation":[{"name":"Department of Morphology Post\u2010Graduation Program in Oral Pathology Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boniek Castillo Dutra","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Dentistry Post\u2010Graduation Program in Public Health Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Sandro Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Dentistry Post\u2010Graduation Program in Public Health Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2015.10.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-015-1720-y"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2015.05.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.22.010305.104258"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-009-0839-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22815"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199810001-00013"},{"key":"e_1_2_7_9_1","first-page":"34","article-title":"Lasers in medicine and biology","volume":"72","author":"Cunningham T.M.","year":"1970","journal-title":"N. 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