These findings concern laboratory and animal models and do not establish clinical efficacy in people. Simvastatin is a lipid-lowering drug, and the study examined its potential to influence osteogenic differentiation and angiogenic regulation during bone-tissue formation. Researchers isolated stem cells from human exfoliated deciduous teeth collected from caries-free teeth.

Cell-based assays measured proliferation, migration, apoptosis, alkaline phosphatase activity, matrix mineralization, gene expression, and protein markers associated with osteogenesis and Wnt/β-catenin signaling. The investigators also measured angiogenic regulatory factors and used a co-culture system to determine whether treated stem cells could promote the formation of vascular networks by endothelial cells. At concentrations of 1 µM or less, simvastatin enhanced migration of the tooth-derived stem cells without adversely affecting cell viability.

Within this range, 0.1 µM simvastatin significantly increased the expression of osteogenic genes. The treated cells also showed greater alkaline phosphatase activity and increased matrix mineralization, consistent with progression toward an osteogenic phenotype. Simvastatin increased the expression of angiogenic regulatory factors in the stem cells, and endothelial cells in the co-culture formed more extensive reticular structures around them.

The researchers also detected increased markers associated with Wnt/β-catenin pathway activation. When dickkopf-related protein 1, or DKK-1, was used to inhibit this pathway, the osteogenic and angiogenic effects attributed to simvastatin were reversed. The inhibition result supports a contributing role for the pathway, although the experiment does not establish it as the sole mechanism or define the complete signaling network.

The researchers then prepared porous hydroxyapatite scaffolds loaded with simvastatin and the tooth-derived stem cells and transplanted them subcutaneously into nude mice. Histological analysis showed that simvastatin-containing scaffolds supported the formation of bone-like tissue together with increased blood vessel formation. Expression of factors associated with osteogenesis and angiogenesis was also enhanced in the transplanted material.

The study’s scope was therefore a coordinated laboratory and animal evaluation of simvastatin-loaded, cell-seeded scaffolds, with the Wnt/β-catenin pathway identified as one mechanism implicated in the observed effects.

Subject of Research: Preclinical effects of simvastatin on osteogenesis, angiogenesis, and Wnt/β-catenin signaling in tooth-derived stem cells

Article Title: Coordinated effect of simvastatin-induced osteogenesis and angiogenesis mediated by Wnt/β-catenin signaling pathway on vascularized bone tissue formation

Article References: Chen, Y., Lu, H., Lin, L., Chen, J., Li, P., Wu, J., Mu, Q., Yu, D., & Zhao, W. (2026). Coordinated effect of simvastatin-induced osteogenesis and angiogenesis mediated by Wnt/β-catenin signaling pathway on vascularized bone tissue formation. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-09093-y

Image Credits: AI Generated

DOI: 10.1186/s12967-026-09093-y

Keywords: simvastatin, osteogenesis, angiogenesis, Wnt/β-catenin signaling, stem cells, bone tissue engineering, endothelial cells, hydroxyapatite scaffolds, vascularized bone, preclinical research, Coordinated, effect