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While the Wnt pathway is pivotal for mediating the osteoblast response to loading, the exact mechanisms are not fully understood. Here, we found that mechanical stimulation induces osteoblastic\n                    <jats:italic>Wnt1<\/jats:italic>\n                    expression, resulting in an upregulation of key osteogenic marker genes, including\n                    <jats:italic>Runx2<\/jats:italic>\n                    and\n                    <jats:italic>Sp7<\/jats:italic>\n                    , while\n                    <jats:italic>Wnt1<\/jats:italic>\n                    knockdown using siRNA prevented these effects. RNAseq analysis identified\n                    <jats:italic>Plat<\/jats:italic>\n                    as a major target through which\n                    <jats:italic>Wnt1<\/jats:italic>\n                    exerts its osteogenic influence. This was corroborated by\n                    <jats:italic>Plat<\/jats:italic>\n                    depletion using siRNA, confirming its positive role in osteogenic differentiation. Moreover, we demonstrated that mechanical stimulation enhances\n                    <jats:italic>Plat<\/jats:italic>\n                    expression, which, in turn leads to increased expression of osteogenic markers like\n                    <jats:italic>Runx2<\/jats:italic>\n                    and\n                    <jats:italic>Sp7<\/jats:italic>\n                    . Notably,\n                    <jats:italic>Plat<\/jats:italic>\n                    depletion by siRNA prevented this effect. We have established that\n                    <jats:italic>Wnt1<\/jats:italic>\n                    regulates\n                    <jats:italic>Plat<\/jats:italic>\n                    expression by activating \u03b2\u2010Catenin. Silencing\n                    <jats:italic>Wnt1<\/jats:italic>\n                    impairs mechanically induced \u03b2\u2010Catenin activation, subsequently reducing\n                    <jats:italic>Plat<\/jats:italic>\n                    expression. Furthermore, our findings showed that\n                    <jats:italic>Wnt1<\/jats:italic>\n                    is essential for osteoblasts to respond to mechanical stimulation and induce\n                    <jats:italic>Runx2<\/jats:italic>\n                    and\n                    <jats:italic>Sp7<\/jats:italic>\n                    expression, in part through the Wnt1\/\u03b2\u2010Catenin\/Plat signaling pathway. Additionally, we observed significantly reduced\n                    <jats:italic>Wnt1<\/jats:italic>\n                    and\n                    <jats:italic>Plat<\/jats:italic>\n                    expression in bones from ovariectomy (OVX)\u2010induced and age\u2010related osteoporotic mouse models compared with non\u2010OVX and young mice, respectively. Overall, our data suggested that\n                    <jats:italic>Wnt1<\/jats:italic>\n                    and\n                    <jats:italic>Plat<\/jats:italic>\n                    play significant roles in mechanically induced osteogenesis. Their decreased expression in bones from OVX and aged mice highlights their potential involvement in post\u2010menopausal and age\u2010related osteoporosis, respectively.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301424rr","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T11:05:01Z","timestamp":1708945501000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-4039","authenticated-orcid":false,"given":"Mubashir","family":"Ahmad","sequence":"first","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics University Medical Center Ulm  Ulm 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