{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:27:46Z","timestamp":1789583266070,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"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":["81771032"],"award-info":[{"award-number":["81771032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Endochondral ossification is essential for the development of appendicular bones, physiological bone remodelling and fracture healing. Recent studies have identified mesenchymal stromal cell\u2010derived FABP5\n                    <jats:sup>+<\/jats:sup>\n                    septoclasts (SCs) as key mediators for the growth and repair of long bones, particularly in cartilage matrix degradation and growth plate remodelling via the secretion of matrix metalloproteinases. Our previous study has shown that soluble epoxide hydrolase (sEH) inhibitor, 1\u2010trifluoromethoxyphenyl\u20103\u2010(1\u2010propionylpiperidin\u20104\u2010yl) urea (TPPU), promotes long bone growth and bone repair by enhancing H\u2010type vessel\u2010coupled osteogenesis. However, whether TPPU treatment regulates SC activity, thereby promoting long\u2010bone growth and fracture healing, remains unclear. Here, our in\u00a0vitro and in\u00a0vivo results showed that TPPU treatment promoted long\u2010bone growth in newborn mice and regulated the hypertrophic layer in the growth plate, with a reduced ratio of hypertrophic cartilage (HC) to proliferative cartilage (PC) width. Furthermore, TPPU treatment enhanced SC activity, as evidenced by elevated expression of MMP9 and FABP5 in the metaphysis near the growth plate. Simultaneously, TPPU induced FABP5\n                    <jats:sup>+<\/jats:sup>\n                    SC\u2010like cells to degrade chondrocytes in co\u2010cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs). Mechanistically, TPPU enhanced the crosstalk of co\u2010cultured HUVECs and hDPSCs to activate the NOTCH signalling pathway in hDPSCs by upregulating HIF\u20101\u03b1 expression in HUVECs. Furthermore, TPPU enhanced fracture healing by inducing more FABP5\n                    <jats:sup>+<\/jats:sup>\n                    SCs and MMP9 secretion at the fracture site. Collectively, these findings highlight sEH as a promising therapeutic target that regulates endochondral ossification through inducing SC activity, offering new opportunities for bone development and repair.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70249","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:44:36Z","timestamp":1781567076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Soluble Epoxide Hydrolase Inhibition Regulates Septoclast Activity to Promote Long Bone Growth and Fracture Healing by Enhancing Endothelial\u2010to\u2010Mesenchymal Notch Signalling"],"prefix":"10.1111","author":[{"given":"Weixian","family":"Chen","sequence":"first","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Yunnan Key Laboratory of Stomatology and Department of Dental Research The Affiliated Stomatology Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9093-661X","authenticated-orcid":false,"given":"Liangliang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xumeng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9819-9665","authenticated-orcid":false,"given":"Juanjuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"National\u2010Local Joint Engineering Research Center for Drug\u2010Research and Development (R&amp;D) of Neurodegenerative Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9615-1038","authenticated-orcid":false,"given":"Fu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Stomatology Dalian Medical University  Dalian China"},{"name":"Academician Laboratory of Immune and Oral Development &amp; Regeneration Dalian Medical University  Dalian China"},{"name":"Stomatological Hospital, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/jbmr\/zjae069","article-title":"Skeletal Stem and Progenitor Cells in Bone Development and Repair","volume":"39","author":"Trompet D.","year":"2024","journal-title":"Journal of Bone and Mineral Research"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"4830","DOI":"10.1016\/j.bioactmat.2021.05.011","article-title":"Articular Cartilage and Osteochondral Tissue Engineering Techniques: Recent Advances and Challenges","volume":"6","author":"Wei W.","year":"2021","journal-title":"Bioactive Materials"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41580-020-00279-w","article-title":"Mechanisms of Bone Development and Repair","volume":"21","author":"Salhotra A.","year":"2020","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.7150\/thno.34126","article-title":"Type H Blood Vessels in Bone Modeling and Remodeling","volume":"10","author":"Peng Y.","year":"2020","journal-title":"Theranostics"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41574-021-00488-z","article-title":"The Role of Biomineralization in Disorders of Skeletal Development and Tooth Formation","volume":"17","author":"Kovacs C. 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