Authors
Jai-Hong Cheng, Chi-Hsiang Hsu, Meng-Lun Tsai, Jeng-Wei Chen, Shun-Wun Jhan, Suhyun Lee, Chien-Yiu Huang, Shan-Ling Hsu
Published in
International journal of medical sciences. Volume 23. Issue 9. Pages 2767-2779. Epub Jul 22, 2026.
Abstract
1α,25(OH)₂D₃ (vitamin D3, VitD3) and extracorporeal shockwave therapy (ESWT) promote osteoblast differentiation and mineralization. Protein disulfide isomerase-associated 3 (Pdia3) mediates rapid membrane signaling of VitD3, but its interaction with ESWT remains unclear.
MC3T3-E1 cells were treated with VitD3, ESWT, or both. Alkaline phosphatase activity and Alizarin red staining assessed osteoblast differentiation and mineralization. Pdia3 expression and signaling were evaluated by Western blotting and ELISA. Pdia3 distribution was analyzed by immunofluorescence and flow cytometry.
The actin polymerization inhibitor latrunculin B tested the role of F-actin. Combined VitD3 and ESWT significantly increased ALP activity, mineral deposition, Pdia3 expression, and plasma membrane localization versus single treatments. These effects were mediated by Pdia3-dependent protein kinase C (PKC) activation. Disruption of F-actin reduced Pdia3 membrane localization and abolished the combined osteogenic effects. ESWT promoted F-actin repolymerization, facilitating Pdia3 trafficking to the membrane.
VitD3 and ESWT exert enhanced combined effects on osteoblast differentiation and mineralization by promoting F-actin mediated Pdia3 membrane localization and activating the PKC pathway. The integrity of the actin cytoskeleton is essential for these effects.
PMID:
42694575
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.
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