{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:22:53Z","timestamp":1773368573827,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aims to develop a novel therapeutic strategy for osteoporosis (OP) by enhancing the osteogenic differentiation potential of mesenchymal stem cells (MSCs). A three\u2010channel biomimetic bone organ\u2010on\u2010a\u2010chip model was constructed. Through bioinformatics analysis,\n                    <jats:italic>TPD52L1<\/jats:italic>\n                    , a key upregulated gene involved in the osteogenic differentiation of MSCs, was identified. Molecular experiments were conducted to verify the effects of its overexpression on the Wnt\/\u03b2\u2010catenin pathway. Critically, systematic knockdown experiments were performed to validate its necessity in mechanotransduction. Subsequently, functional experiments were performed to evaluate its role in the osteogenic and adipogenic differentiation of MSCs in a GIOP model. Safety assessments for\n                    <jats:italic>TPD52L1\u2010<\/jats:italic>\n                    overexpressing MSCs covered subcellular localization, proliferation, anchorage\u2010independent growth, oncogene expression, and short\u2010term in\u00a0vivo tumorigenicity.\n                    <jats:italic>TPD52L1<\/jats:italic>\n                    overexpression activated the Wnt\/\u03b2\u2010catenin pathway and promoted osteogenic differentiation of MSCs. Its knockdown blocked mechanical stimulation\u2010induced pathway activation and osteogenic marker upregulation, confirming its necessity in mechano\u2010osteogenic conversion.\n                    <jats:italic>TPD52L1<\/jats:italic>\n                    upregulated osteoblast markers osteocalcin (OCN) and alkaline phosphatase (ALP), downregulated the osteoclast marker tartrate\u2010resistant acid phosphatase (TRAP), and reversed the osteoporosis phenotype. When combined with cyclic mechanical force stimulation in the organ\u2010on\u2010a\u2010chip system, a synergistic effect was observed, enhancing bone repair.\n                    <jats:italic>TPD52L1<\/jats:italic>\n                    was localized in the cytoplasm, and its endogenous expression was upregulated by mechanical stimulation, indicating mechanosensitivity.\n                    <jats:italic>TPD52L1<\/jats:italic>\n                    overexpression did not affect MSCs' proliferation, anchorage\u2010independent growth, or oncogene expression. Subcutaneous transplantation experiments confirmed that it did not induce tumor formation or significant pathological changes, demonstrating favorable biosafety. TPD52L1 serves as a key target for promoting the osteogenic differentiation of MSCs.\n                  <\/jats:p>","DOI":"10.1096\/fj.202503575rr","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T11:21:04Z","timestamp":1770463264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bone Organ\u2010on\u2010a\u2010Chip Uncovers That\n                    <scp>TPD52L1<\/scp>\n                    Enhances Osteogenic Differentiation of\n                    <scp>MSCs<\/scp>\n                    and Contributes to Osteoporosis Repair"],"prefix":"10.1096","volume":"40","author":[{"given":"Zhewen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Traumatology The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weina","family":"Ju","sequence":"additional","affiliation":[{"name":"Department 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