Zinc promotes osteogenesis through enhanced preosteoblast proliferation, osteogenic differentiation, and bone-related transcriptomic remodeling

Zinc (Zn) is an essential trace element that contributes to skeletal development, bone remodeling, and mineral homeostasis, yet the molecular mechanisms underlying its effects on osteoblast differentiation remain incompletely defined. This study investigated the effects of Zn ions on preosteoblast growth and osteogenic differentiation and characterized Zn-responsive transcriptomic changes. Under osteogenic conditions, Zn increased alkaline phosphatase activity, mineralized matrix formation, and expression of osteogenic markers, including alkaline phosphatase (ALP), osteocalcin, procollagen I, and Runx2. RNA sequencing identified over a thousand differentially expressed genes following Zn²⁺ treatment. Functional enrichment analysis revealed modulation of bone-related pathways, including Wnt, TGF-β/BMP, Hippo, and PI3K-Akt signaling, as well as extracellular matrix (ECM)-receptor interaction, focal adhesion, and osteoclast differentiation. Transcriptomic analysis highlighted osteogenesis-associated candidate genes, including Wnt16, Lrp6, Bmp6, and Tnfrsf11b. Together, these findings associate Zn-enhanced osteogenic responses with changes in bone-related gene expression and identify candidate signaling relationships for future functional investigation.