{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:10:27Z","timestamp":1778220627432,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,8]]},"group-title":"Cell Biology","reference-count":26,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R01DE033511"],"award-info":[{"award-number":["R01DE033511"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorder and Stroke","doi-asserted-by":"crossref","award":["RF1NS137467"],"award-info":[{"award-number":["RF1NS137467"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorder and Stroke","doi-asserted-by":"crossref","award":["R01NS136377"],"award-info":[{"award-number":["R01NS136377"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The anatomical localization of lymphatic vessels in bone remains controversial and has led to conflicting interpretations of skeletal lymphatic function. Here we assessed lymphatic identity and localization in bone using mouse genetic labeling, tissue clearance, and three-dimensional imaging. We analyzed long bones after extensive periosteum removal and identified Vegfr3\n                  <jats:sup>+<\/jats:sup>\n                  blood vessels lacking Lyve1 expression within bone marrow, whereas Vegfr3\n                  <jats:sup>+<\/jats:sup>\n                  Lyve1\n                  <jats:sup>+<\/jats:sup>\n                  lymphatic vessels were confined to residual periosteal regions. Genetic lineage tracing using Prox1-Cre\/ER;mScarlet further confirmed that lymphatic vessels are absent from long bone marrow and restricted to periosteal compartments, particularly in fibrous but not cambial layers. Extending these analyses to the mandible, we observed Vegfr3\n                  <jats:sup>+<\/jats:sup>\n                  Lyve1\n                  <jats:sup>+<\/jats:sup>\n                  lymphatic vessels localized to periarticular soft tissues surrounding the temporomandibular joint (TMJ), while mandibular bone marrow contained only Vegfr3\n                  <jats:sup>+<\/jats:sup>\n                  Lyve1\n                  <jats:sup>\u2212<\/jats:sup>\n                  blood vessels and lacked Prox1 lineage-traced lymphatic vessels. Together, these findings establish that lymphatic vessels in bone are confined to periosteal and periarticular compartments and absent from bone marrow, providing a framework for interpreting lymphatic contributions to skeletal physiology and disease.\n                <\/jats:p>","DOI":"10.64898\/2026.04.06.716745","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:35:17Z","timestamp":1775806517000},"source":"Crossref","is-referenced-by-count":0,"title":["Periosteal and periarticular compartments house lymphatic vessels in bone"],"prefix":"10.64898","author":[{"given":"Qing","family":"Chang","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Shu","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pao-Fen","family":"Ko","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050722151464000_2026.04.06.716745v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(88)90084-2"},{"issue":"1","key":"2026050722151464000_2026.04.06.716745v1.2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1445-2197.1964.tb03976.x","article-title":"LYMPHATIC DRAINAGE OF BONE MARROW","volume":"34","year":"1964","journal-title":"Aust N Zealand J Surg"},{"issue":"15","key":"2026050722151464000_2026.04.06.716745v1.3","first-page":"e149831","article-title":"KRAS-driven model of Gorham-Stout disease effectively treated with trametinib","volume":"6","year":"2021","journal-title":"JCI Insight"},{"issue":"5","key":"2026050722151464000_2026.04.06.716745v1.4","doi-asserted-by":"crossref","first-page":"694","DOI":"10.5312\/wjo.v5.i5.694","article-title":"Vanishing bone disease (Gorham-Stout syndrome): A review of a rare entity","volume":"5","year":"2014","journal-title":"World J Orthop"},{"key":"2026050722151464000_2026.04.06.716745v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.031"},{"issue":"1","key":"2026050722151464000_2026.04.06.716745v1.6","first-page":"54e","article-title":"Craniofacial and Long Bone Development in the Context of Distraction Osteogenesis","volume":"147","year":"2020","journal-title":"Plast Reconstr Surg"},{"key":"2026050722151464000_2026.04.06.716745v1.7","doi-asserted-by":"publisher","DOI":"10.1177\/10454411000110010101"},{"issue":"9","key":"2026050722151464000_2026.04.06.716745v1.8","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/jopr.13203","article-title":"The Temporomandibular Joint: A Critical Review of Life-Support Functions, Development, Articular Surfaces, Biomechanics and Degeneration","volume":"29","year":"2020","journal-title":"J Prosthodont"},{"key":"2026050722151464000_2026.04.06.716745v1.9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/bs.ctdb.2018.12.013","article-title":"Chapter Four Regulatory mechanisms of jaw bone and tooth development","volume":"133","year":"2019","journal-title":"Curr Top Dev Biol"},{"issue":"5","key":"2026050722151464000_2026.04.06.716745v1.10","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1007\/s11914-023-00804-8","article-title":"Cranial Neural Crest Cells Contribution to Craniofacial Bone Development and Regeneration","volume":"21","year":"2023","journal-title":"Curr Osteoporos Rep"},{"key":"2026050722151464000_2026.04.06.716745v1.11","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1152301"},{"issue":"12","key":"2026050722151464000_2026.04.06.716745v1.12","doi-asserted-by":"crossref","first-page":"e20241971","DOI":"10.1084\/jem.20241971","article-title":"Identification of lymphatic vessels in skull periosteum but not bone marrow reveals skull channel heterogeneity","volume":"222","year":"2025","journal-title":"J Exp Med"},{"key":"2026050722151464000_2026.04.06.716745v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5390.946"},{"key":"2026050722151464000_2026.04.06.716745v1.14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.310477"},{"key":"2026050722151464000_2026.04.06.716745v1.15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-298562"},{"key":"2026050722151464000_2026.04.06.716745v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2024.03.019"},{"key":"2026050722151464000_2026.04.06.716745v1.17","doi-asserted-by":"crossref","unstructured":"Chen J-F , et al. Identification of Synovial Lymphatics in the TMJ and their Roles in Arthritis and Pain. Res Sq. 2025;rs.3.rs-6683299.","DOI":"10.21203\/rs.3.rs-6683299\/v1"},{"issue":"3","key":"2026050722151464000_2026.04.06.716745v1.18","doi-asserted-by":"crossref","first-page":"e184379","DOI":"10.1172\/jci.insight.184379","article-title":"Mapping cell diversity and dynamics in inflammatory temporomandibular joint osteoarthritis with pain at single-cell resolution","volume":"10","year":"2025","journal-title":"JCI Insight"},{"key":"2026050722151464000_2026.04.06.716745v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.04.022"},{"issue":"2","key":"2026050722151464000_2026.04.06.716745v1.20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1089\/ten.teb.2022.0076","article-title":"Collision of Commonality and Personalization: Better Understanding of the Periosteum","volume":"29","year":"2023","journal-title":"Tissue Eng Part B: Rev"},{"issue":"1","key":"2026050722151464000_2026.04.06.716745v1.21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13062-021-00310-w","article-title":"The periosteum: a simple tissue with many faces, with special reference to the antler-lineage periostea","volume":"16","year":"2021","journal-title":"Biol Direct"},{"key":"2026050722151464000_2026.04.06.716745v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20833"},{"key":"2026050722151464000_2026.04.06.716745v1.23","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515574770"},{"key":"2026050722151464000_2026.04.06.716745v1.24","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.859517"},{"issue":"3","key":"2026050722151464000_2026.04.06.716745v1.25","doi-asserted-by":"crossref","first-page":"e191906","DOI":"10.1172\/JCI191906","article-title":"Targeting lymphatic vessels enhances bone regeneration by augmenting osteoclast activity in mouse models of amputation","volume":"136","year":"2026","journal-title":"J Clin Investig"},{"issue":"4","key":"2026050722151464000_2026.04.06.716745v1.26","doi-asserted-by":"crossref","first-page":"114049","DOI":"10.1016\/j.celrep.2024.114049","article-title":"Vegfc-expressing cells form heterotopic bone after musculoskeletal injury","volume":"43","year":"2024","journal-title":"Cell Rep"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.06.716745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:15:35Z","timestamp":1778217335000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.06.716745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":26,"URL":"https:\/\/doi.org\/10.64898\/2026.04.06.716745","relation":{},"subject":[],"published":{"date-parts":[[2026,4,8]]},"subtype":"preprint"}}