PDLIM2 Promotes Osteogenesis of Adipose-Derived Stem Cells by Modulating β-Actin-Dependent Wnt/β-Catenin Signaling

Bone tissue possesses strong regenerative potential, but large segmental bone defects often exceed its intrinsic capacity for self-healing. Human adipose-derived stem cells (hASCs) offer a promising cellular basis for bone regeneration owing to their robust osteogenic differentiation potential. However, the role of PDZ and LIM domain 2 (PDLIM2) play in hASC osteogenesis and its relationship with the Wnt/β-catenin signaling pathway remain poorly understood.

Western blotting, immunofluorescence staining, Alizarin Red S staining, alkaline phosphatase activity assays, wound healing assays, and Transwell assays were employed to assess osteogenic differentiation, osteogenic capacity, and cellular migration. Lentivirus-mediated PDLIM2 knockdown, cytochalasin D (CytoD) intervention, microfilament stabilizer treatment, and β-catenin activator treatment were used as a means of validating the regulatory mechanism.

hASCs exhibited the ability to undergo osteogenic differentiation. During this osteogenic process, significant increases in PDLIM2, β-actin, and β-catenin expression were observed, with PDLIM2 expression reaching 2-3 times that of the control group on day 14, whereas β-actin and β-catenin levels peaked on day 7 (1.5-2 times those in the control group). Lentivirus-mediated PDLIM2 knockdown reduced β-actin expression by approximately 5-fold and β-catenin expression by approximately 1.7-fold, accompanied by cytoskeletal disorganization and impaired osteogenic differentiation. Actin microfilament integrity was found to regulate osteogenic marker expression and alkaline phosphatase activity, while CytoD treatment suppressed β-actin and β-catenin expression to approximately 50% of control levels and inhibited osteogenic differentiation. Knocking down PDLIM2 attenuated the responsiveness of hASCs to microfilament stabilizers and β-catenin activators.

This study demonstrates that PDLIM2 may be functionally associated with β-catenin nuclear translocation, potentially through the remodeling of the actin cytoskeleton. These findings provide preliminary mechanistic insight and warrant further validation.