{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:36:10Z","timestamp":1790840170466,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR069620"],"award-info":[{"award-number":["AR069620"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Masquelet induced\u2010membrane (IM) technique is indicated for large segmental bone defects. Attributes of the IM and local milieu that contribute to graft\u2010to\u2010bone union are unknown. Using a rat model, we compared global gene expression profiles in critically sized femoral osteotomies managed using a cement spacer as per Masquelet to those left empty. At the end of the experiment, IM and bone adjacent to the spacer were collected from the Masquelet side. Nonunion tissue in the defect and bone next to the empty defect were collected from the contralateral side. Tissues were subjected to RNA isolation, sequencing, and differential expression analysis. Cell type enrichment analysis suggested the IM and the bone next to the polymethylmethacrylate (PMMA) spacer were comparatively enriched for osteoblastic genes. The nonunion environment was comparatively enriched for innate and adaptive immune cell markers, but only macrophages were evident in the Masquelet context. iPathwayGuide was utilized to identify cell signaling pathways and protein interaction networks enriched in the Masquelet environment. For IM vs nonunion false\u2010discovery rate correction of <jats:italic>P<\/jats:italic> values rendered overall pathway differences nonsignificant, and so only protein interaction networks are presented. For the bone comparison, substantial enrichment of pathways and networks known to contribute to osteogenic mechanisms was revealed. Our results suggest that the PMMA spacer affects the cut bone ends that are in contact with it and at the same time induces the foreign body reaction and formation of the IM. B cells in the empty defect suggest a chronic inflammatory response to a large segmental osteotomy.<\/jats:p>","DOI":"10.1002\/jor.24676","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T11:35:50Z","timestamp":1585654550000},"page":"2120-2130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation of global gene expression in regenerate tissues during Masquelet treatment"],"prefix":"10.1002","volume":"38","author":[{"given":"Nishant","family":"Gohel","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Senos","sequence":"additional","affiliation":[{"name":"Department of Morphology Universidade Federal Fluminense  Niteroi Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt D.","family":"Hankenson","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Hake","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8568-7152","authenticated-orcid":false,"given":"Andrea I.","family":"Alford","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2014.04.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocl.2009.07.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.L.00310"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0000000000000614"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(16)30842-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0000000000000981"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9020450"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(03)00165-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-81"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.1921"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e3182691288"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.54.2000483"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22047"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.1826"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0274"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22815"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-012-9580-y"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-460"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23652"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn577"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14351"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-019-01217-y"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.99B5.BJJ-2016-0694.R2"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2019.06.018"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.34495"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.07.006"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.12.025"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2422"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.354"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.08.017"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.08.009"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.185"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24186"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004754"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2019.06.007"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2018.01.001"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.044"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-018-02137-5"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2018.06.041"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23866"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.24676","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24676","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.24676","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24676","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:50:14Z","timestamp":1693921814000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.24676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,6]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1002\/jor.24676"],"URL":"https:\/\/doi.org\/10.1002\/jor.24676","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,6]]},"assertion":[{"value":"2019-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}