Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling

TLDR

Strontium ranelate and strontium‑containing hydroxyapatite reduce fracture risk by boosting bone formation and suppressing resorption through osteoblast activation and osteoclast inhibition. The study aimed to elucidate the molecular mechanisms by which strontium promotes bone formation. Researchers examined strontium’s effects on human mesenchymal stem cell osteogenic differentiation and assessed its osteogenic potential in a rat calvarial defect model. Strontium enhanced MSC osteogenic differentiation by upregulating extracellular matrix genes and activating the Wnt/β‑catenin pathway, and in vivo implantation of a strontium‑substituted hydroxyapatite scaffold markedly increased mature bone formation and β‑catenin expression, demonstrating a novel mechanism for its bone‑forming activity.

Abstract

Abstract Strontium ranelate is a newly approved drug that can reduce the risk of vertebral fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. Strontium-containing hydroxyapatite was also demonstrated to stimulate the osteoblast activity and inhibit the osteoclast activity. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood. In this study, we investigated the effects of strontium on the osteogenic differentiation of human mesenchymal stem cells (MSCs) and its related mechanism; its osteogenic potential was also evaluated using a calvarial defect model in rats. We found that strontium could enhance the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/β-catenin pathway. After transplanting the collagen-strontium-substituted hydroxyapatite scaffold into the bone defect region, histology and computed tomography scanning revealed that in vivo bone formation was significantly enhanced; the quantity of mature and remodeled bone substantially increased and ECM accumulated. Interestingly, strontium induced an increase of β-catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the β-catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation.