{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:24:32Z","timestamp":1787203472903,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008288","name":"Alborada Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bone fractures in Thoroughbred racehorses are a major welfare problem. Genetic factors contribute to fracture risk. Cell models have previously identified 112 differentially expressed genes in bone\u2010forming osteoblasts derived from horses at high and low genetic risk of fracture. However, 42 of these genes have no published role in bone. In this study, we identified novel roles for a subset of these genes in bone formation. Twenty\u2010six of the 42 genes were expressed in Saos2 cells during basal culture and\/or after 21\u2009days of osteogenic culture. Five of these genes (\n                    <jats:italic>ADSSL1<\/jats:italic>\n                    ,\n                    <jats:italic>CABP1<\/jats:italic>\n                    ,\n                    <jats:italic>ENO2<\/jats:italic>\n                    ,\n                    <jats:italic>SPARCL1<\/jats:italic>\n                    and\n                    <jats:italic>UCP2<\/jats:italic>\n                    ) were then stably overexpressed and knocked down, and their effect on osteogenesis was measured. Gene overexpression resulted in significant decreases in Saos2 cell viability and decreased expression of osteogenic genes under basal cell culture, but after 21\u2009days of osteogenic culture there were few significant changes in osteogenic gene expression, collagen deposition or matrix mineralisation. Knockdown of\n                    <jats:italic>SPARCL1<\/jats:italic>\n                    resulted in total cell death, whereas knockdown of\n                    <jats:italic>ADSSL1<\/jats:italic>\n                    ,\n                    <jats:italic>CABP1<\/jats:italic>\n                    ,\n                    <jats:italic>ENO2<\/jats:italic>\n                    and\n                    <jats:italic>UCP2<\/jats:italic>\n                    resulted in decreased cell viability but limited significant changes in osteogenic gene expression under basal cell culture. However, following osteogenic culture, gene knockdown induced widespread changes in osteogenic gene expression, decreased collagen deposition and increased matrix mineralisation.\n                    <jats:italic>ADSSL1<\/jats:italic>\n                    ,\n                    <jats:italic>CABP1<\/jats:italic>\n                    ,\n                    <jats:italic>ENO2<\/jats:italic>\n                    and\n                    <jats:italic>UCP2<\/jats:italic>\n                    were all expressed at significantly lower levels in osteoblasts from genetically high\u2010risk horses. Taken together, this work demonstrates novel roles for fracture\u2010associated genes in bone formation and matrix mineralisation suggesting these processes may be altered in genetically susceptible horses.\n                  <\/jats:p>","DOI":"10.1002\/age.70166","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:35:12Z","timestamp":1783524912000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genes Associated With Fracture Risk in Thoroughbred Horses Have Novel Roles in Osteogenesis"],"prefix":"10.1002","volume":"57","author":[{"given":"Amy C.","family":"Ross","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Services, Centre for Vaccinology and Regenerative Medicine The Royal Veterinary College  Hatfield Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellison S.","family":"Lumsden","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Services, Centre for Vaccinology and Regenerative Medicine The Royal Veterinary College  Hatfield Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Flood","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Services, Centre for Vaccinology and Regenerative Medicine The Royal Veterinary College  Hatfield Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-697X","authenticated-orcid":false,"given":"Jayesh","family":"Dudhia","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Services, Centre for Vaccinology and Regenerative Medicine The Royal Veterinary College  Hatfield Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Androniki","family":"Psifidi","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Services, Centre for Vaccinology and Regenerative Medicine The Royal Veterinary College  Hatfield Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0034-3332","authenticated-orcid":false,"given":"Deborah J.","family":"Guest","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Services, Centre for Vaccinology and Regenerative Medicine The Royal Veterinary College  Hatfield Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701116200"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13470"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.08.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2012.2963"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-147"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.77.1.32"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.021"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200397R"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44324-024-00010-9"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008361"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/382448a0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2016.11.013"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2016.12.006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092240208"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10100745"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes7110097"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005282"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3410537"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.12544"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008586"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2007.0334"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani13050827"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani14010116"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2026.106573"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.13504"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2024.117048"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.5.1447"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/tvjl.2001.0610"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021119-034332"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194299"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20253890"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.02.001"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.13291"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21364"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14010121"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01060"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12866"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jbg.12387"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010159"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2014.03.005"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.14046"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-021-04272-y"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16142503"}],"container-title":["Animal Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/age.70166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/age.70166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/age.70166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:48:40Z","timestamp":1787201320000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/age.70166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/age.70166"],"URL":"https:\/\/doi.org\/10.1002\/age.70166","archive":["Portico"],"relation":{},"ISSN":["0268-9146","1365-2052"],"issn-type":[{"value":"0268-9146","type":"print"},{"value":"1365-2052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"2026-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70166"}}