Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential

This study explores the potential of zinc valproic acid (Z-VA) complex as a promoter of osteoblast differentiation and a preventive agent against osteoporosis. The concentration of 25 µM Z-VA improved osteoblast differentiation by increasing the expression of Runx2 and type 1 collagen mRNA, alkaline phosphatase activity, and cellular calcium deposition. Dexamethasone-induced osteoporosis models were used in zebrafish and rats. In the zebrafish scale regeneration model, Z-VA decreased the hydroxyproline content and tartrate-resistant acid phosphatase activity while also upregulating the calcium to phosphorus molar ratio, Runx2a MASNA isoform, collagen2α, osteocalcin, and osteonectin. Additionally, Z-VA upregulated osteopontin and mitogen-activated protein kinase expression and downregulated matrix metalloproteinase 3 expression. Z-VA increased calcium deposition, callus formation, and bone growth in a zebrafish fracture model. In the rat model, Z-VA increased the bone transverse diameter, length, weight, mineral content, and mineral density, as well as serum Ca²⁺, inorganic phosphate, interleukin-6, tumor necrosis factor alpha, and alkaline phosphatase. Our results suggest that Z-VA may be an effective anti-osteoporotic agent that stimulates bone growth and prevents bone loss. However, further research is needed to elucidate its mechanisms and enhance its therapeutic application.