{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T15:35:37Z","timestamp":1780673737283,"version":"3.54.1"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Musculoskeletal malignancy is often accompanied by aberrant bone remodeling, leading to tumor cell invasion into skeletal tissues and causing severe pain. BMPs, FGF\u20102, and RANKL have been identified as promising regulators in physiological bone remodeling. In this study, we explored the expressional profile of BMPs, FGF\u20102, and RANKL in 1361 patients with 22 varieties of musculoskeletal tumors. Notably, the expression of FGF\u20102 and RANKL was under detected in all patients. Among BMP1 to BMP15, we found that BMP1, BMP2, BMP4, BMP5, BMP6, and BMP7 were prevalent. In comparison with normal bones, osteosarcoma highly expressed BMP1, BMP2, BMP4, and BMP7 with statistical significance. Synovial sarcoma upregulated BMP4, BMP5, and BMP7; rhabdomyosarcoma increased BMP1 and BMP4; and alveolar soft part sarcoma upregulated BMP1, BMP4, and BMP7. To visualize the BMP\u2010oriented interactions in a bone tumor microenvironment, we have developed novel software that analyzes numerous cell\u2010to\u2010cell and ligand\u2010to\u2010receptor interactions, that is, Environmentome, delineating that osteosarcoma\u2010secreted BMP\u20104 and synovial sarcoma\u2010secreted BMP7 potently interact with osteoblasts, osteocytes, osteoclast precursors, and mature osteoclasts. Specifically, quantification analysis revealed that the relationship between osteosarcoma and mature osteoclast\/precursor, BMP4\u2013BMPR2 and BMP4\u2013ACVR2A interactions were most potent. Regarding the association between osteosarcoma and osteocyte\/osteoblast, BMP4\u2013ACVR1 and BMP4\u2013BMPR2 were the key interactions. In the connection between synovial sarcoma and mature osteoclast\/precursor, BMP7\u2013ACVR2A and BMP7\u2013BMPR2 interactions were most remarkable. With regard to the cellular link between synovial sarcoma and osteocyte\/osteoblast, BMP7\u2013BMPR2 was identified as a potent interaction. In conclusion, our new outlook suggests delivering the pathological events that clinically underlie behind severe skeletal pain or fracture in musculoskeletal tumors.<\/jats:p>","DOI":"10.1002\/jor.24879","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T13:47:42Z","timestamp":1602251262000},"page":"1402-1410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular profiling of bone remodeling occurring in musculoskeletal tumors"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4352-7817","authenticated-orcid":false,"given":"Kosei","family":"Nakajima","sequence":"first","affiliation":[{"name":"Division of Translational Research, Exploratory Oncology Research &amp; Clinical Trial Center National Cancer Center Research Institute,\u00a0Chuo\u2010ku  Tokyo Japan"},{"name":"Division of Veterinary Oncology and Orthopedic Surgery, Faculty of Veterinary Medicine, Imabari Campus Okayama University of Science  Imabari Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruki","family":"Kidani","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1793"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2014.09.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-016-9622-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.0017"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2014.0053"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq209"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq223"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200212000-00001"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.146"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.7101"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62344-6"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1324"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3254"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.23"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8866"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2005.07.035"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2019.100207"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060411"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24879","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.24879","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24879","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T03:42:02Z","timestamp":1693366922000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.24879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/jor.24879"],"URL":"https:\/\/doi.org\/10.1002\/jor.24879","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"2020-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}