Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat

• DOI: 10.1096/fj.202301424rr
• Publication Date: 2024-02-26T16:05:01Z
• Authors: Mubashir Ahmad; Melanie Haffner‐L...; Astrid Schoppa; Zeynab Najafova; Teodora Lukic; Timur Alexander Y...; Michael Amling; Thorsten Schinke; Anita Ignatius
• Keywords: RUNX2

Abstract Physical activity‐induced mechanical stimuli play a crucial role in preserving bone mass and structure by promoting formation. While the Wnt pathway is pivotal for mediating osteoblast response to loading, exact mechanisms are not fully understood. Here, we found that stimulation induces osteoblastic Wnt1 expression, resulting an upregulation of key osteogenic marker genes, including Runx2 Sp7 , while knockdown using siRNA prevented these effects. RNAseq analysis identified Plat as major target through which exerts its influence. This was corroborated depletion siRNA, confirming positive differentiation. Moreover, demonstrated enhances which, turn leads increased expression markers like . Notably, this effect. We have established regulates activating β‐Catenin. Silencing impairs mechanically induced β‐Catenin activation, subsequently reducing expression. Furthermore, our findings showed essential osteoblasts respond induce part Wnt1/β‐Catenin/Plat signaling pathway. Additionally, observed significantly reduced bones from ovariectomy (OVX)‐induced age‐related osteoporotic mouse models compared with non‐OVX young mice, respectively. Overall, data suggested significant roles osteogenesis. Their decreased OVX aged mice highlights their potential involvement post‐menopausal osteoporosis,