{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:23:46Z","timestamp":1788531826816,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172384"],"award-info":[{"award-number":["82172384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972039"],"award-info":[{"award-number":["81972039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372370"],"award-info":[{"award-number":["82372370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2021B1515020080"],"award-info":[{"award-number":["2021B1515020080"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022TFC2502901"],"award-info":[{"award-number":["2022TFC2502901"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2502902"],"award-info":[{"award-number":["2022YFC2502902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2502903"],"award-info":[{"award-number":["2022YFC2502903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2502904"],"award-info":[{"award-number":["2022YFC2502904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pathological new bone formation is the main cause of disability in ankylosing spondylitis (AS), and so far, it lacks a targeted therapy. Macrophages are central orchestrators of inflammation progression and tissue remodeling, but their contribution to pathological new bone formation has largely not been explored. Here, it is identified that TREM2\n                    <jats:sup>+<\/jats:sup>\n                    macrophages predominated within the sites of new bone formation and adjacent to osteogenic precursor cells. In vivo, both depletion of macrophages and knockout of Trem2 significantly reduced pathological new bone formation in a collagen antibody\u2010induced arthritis (CAIA) model. Specifically, TREM2\n                    <jats:sup>+<\/jats:sup>\n                    macrophages promoted osteogenic differentiation of ligament\u2010derived progenitor cells (LDPCs) by secreting CREG1, a secretory glycoprotein involved in cell differentiation and normal physiology. CREG1\u2010IGF2R\u2010PI3K\u2010AKT signaling pathway is involved in TREM2\n                    <jats:sup>+<\/jats:sup>\n                    macrophage\u2010mediated pathological new bone formation. In addition, it is found that IL\u201033 promoted TREM2\n                    <jats:sup>+<\/jats:sup>\n                    macrophage differentiation through phosphorylation of STAT6. Targeting the above signalings alleviated new bone formation in the CAIA model. The findings highlight the critical role of IL\u201033\u2010induced TREM2\n                    <jats:sup>+<\/jats:sup>\n                    macrophages in pathological new bone formation and provide potential therapeutic targets for halting spinal ankylosis in AS.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500952","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T03:21:01Z","timestamp":1742181661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["IL\u201033\u2010Induced TREM2\n                    <sup>+<\/sup>\n                    Macrophages Promote Pathological New Bone Formation Through CREG1\u2010IGF2R Axis in Ankylosing Spondylitis"],"prefix":"10.1002","volume":"12","author":[{"given":"Wenjun","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Pediatric Orthopaedics Beijing Jishuitan Hospital Capital Medical University  Beijing 102200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianru","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zemin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongping","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tangming","family":"Guan","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute Guangdong Key Laboratory of Laboratory Animals  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Virology Department of Pathogen Biology and Biosecurity Key Laboratory of Tropical Disease Control of Ministry of Education Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wende","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute Guangdong Key Laboratory of Laboratory Animals  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-402X","authenticated-orcid":false,"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"Guangdong Province Key Laboratory of Orthopaedics and Traumatology  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31591-4"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221035"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737167.2015.1001370"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.156"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24025"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00761-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221406"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00625-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41206"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40468"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40770"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3324"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00675-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.6.534"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.2.135"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.07.028"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.014"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12616"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300339"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi4528"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abo2787"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06685-2"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35166-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add2632"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.06.004"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034339"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.12.001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203643"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiad054"},{"key":"e_1_2_9_32_1","first-page":"193","volume":"16","author":"Gracey E.","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"e_1_2_9_33_1","volume":"24","author":"Wang E. C. E.","year":"2019","journal-title":"Cell Stem Cell"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.054"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1631-3"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add8945"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00837-1"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01475-4"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505071102"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13427"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2022.03.001"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.133298"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402804"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.006"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.95"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012718"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.032444"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100184"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.01.001"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.021"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13380"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20240103"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202500952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202500952","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202500952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:49:05Z","timestamp":1788529745000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202500952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":52,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/advs.202500952"],"URL":"https:\/\/doi.org\/10.1002\/advs.202500952","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"assertion":[{"value":"2025-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2500952"}}