Mechanotransduction Mediated by PDLIM5: The Critical Role of Serpin E2/Integrin β3-Cytoskeleton-Nucleoskeleton Axis in Mechanical Osteogenic Programming.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Despite the regenerative and self-repair capabilities of bone tissues, significant bone loss can result in substantial bone defects. This study was aimed at investigating the role and underlying mechanisms of the mechanosensitive protein PDZ and LIM Domain 5 (PDLIM5) in the osteogenic differentiation of human adipose-derived stem cells (hASCs) under cyclic tensile stress conditions relevant to bone tissue repair. Utilising proteomics and single-cell RNA sequencing, we identified PDLIM5 and serpin E2 as key genes associated with the osteogenic differentiation of stem cells. To evaluate the expression levels of these genes and related proteins, we utilised western blotting, immunofluorescence and alkaline phosphatase (ALP) staining. Furthermore, lentiviral transfection, Cell Counting Kit-8 (CCK-8) assays, transwell migration assays, wound healing assays and protein-protein interaction analyses were conducted to evaluate changes in osteogenic differentiation under both chemical and physical stimuli, as well as to explore the relationship between serine protease inhibitor E2 (serpin E2) and its downstream effector, PDLIM5. The interactions among serpin E2, integrin β3 and PDLIM5 were confirmed through Haematoxylin and Eosin (H&E) staining, immunohistochemistry and immunofluorescence staining of bone tissues and primary adipose-derived stem cells isolated from integrin β3 knockout m

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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