{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:20:59Z","timestamp":1787754059519,"version":"build-2784847793"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,21]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Neurofibromatosis type 1 (NF1) is a genetic condition predisposing children to fracture pseudarthroses. MEK inhibitors are U.S. Food and Drug Administration\u2013approved or are under study for the treatment of malignant pathologies associated with NF1. However, their potential to treat pseudarthrosis is largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Primary cells cultured from control bone or fracture pseudarthroses from children with NF1 were treated with vehicle or with the MEK inhibitors trametinib or selumetinib. Gene expression was evaluated with use of transcriptome sequencing (RNAseq), and the activation of the downstream signaling pathway was evaluated with use of western blotting. Results were replicated in an independent cohort of patient fracture pseudarthrosis-derived primary cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Pseudarthrosis samples were reproducibly associated with the reduced expression of gene signatures implicated in osteoblast differentiation, skeletal development, and the formation of the extracellular matrix. The expression of these gene signatures was significantly rescued following treatment with MEK inhibitors and concomitant reduced MEK\/ERK (MAPK) pathway activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our study identified molecular signatures associated with fracture pseudarthrosis that were rescued with MEK inhibitor treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>MEK inhibitors may promote the healing of fracture pseudarthroses in children with NF1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.24.01007","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T04:46:00Z","timestamp":1743655560000},"page":"1098-1106","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Evidence Supporting MEK Inhibitor Therapy in NF1 Pseudarthrosis"],"prefix":"10.2106","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4994-737X","authenticated-orcid":false,"given":"Nandina","family":"Paria","sequence":"first","affiliation":[{"name":"Center for Translational Research, Scottish Rite for Children, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3934-0009","authenticated-orcid":false,"given":"Ila","family":"Oxendine","sequence":"additional","affiliation":[{"name":"Center for Translational Research, Scottish Rite for Children, Dallas, 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Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-2194","authenticated-orcid":false,"given":"Carol A.","family":"Wise","sequence":"additional","affiliation":[{"name":"Center for Translational Research, Scottish Rite for Children, Dallas, Texas"},{"name":"Department of Orthopaedic Surgery, UT Southwestern Medical Center, Dallas, Texas"},{"name":"McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas"},{"name":"Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0969-2184","authenticated-orcid":false,"given":"Jonathan J.","family":"Rios","sequence":"additional","affiliation":[{"name":"Center for Translational Research, Scottish Rite for Children, Dallas, Texas"},{"name":"Department of Orthopaedic Surgery, UT Southwestern Medical Center, Dallas, Texas"},{"name":"McDermott 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