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

This study investigates the potential of the zinc–valproic acid (Z-VA) complex as a promoter of osteoblast differentiation and a preventive agent against osteoporosis. Treatment with 25 µM Z-VA enhanced osteoblast differentiation, as evidenced by increased mRNA expression of Runx2 and type I collagen, elevated alkaline phosphatase (ALP) activity, and greater cellular calcium deposition. Dexamethasone-induced osteoporosis models in zebrafish and rats were used to evaluate its in vivo effects. In the zebrafish scale regeneration model, Z-VA reduced hydroxyproline levels and tartrate-resistant acid phosphatase (TRAP) activity, while increasing the calcium-to-phosphorus molar ratio and upregulating key osteogenic markers, including the Runx2a MASNA isoform, collagen2α, osteocalcin, and osteonectin. It also GSK2830371 enhanced osteopontin and MAPK expression and suppressed matrix metalloproteinase 3 (MMP3). In a zebrafish fracture model, Z-VA promoted calcium deposition, callus formation, and bone growth. Similarly, in the rat model, Z-VA treatment led to increases in bone transverse diameter, length, weight, mineral content, and mineral density, along with elevated serum levels of calcium, inorganic phosphate, IL-6, TNF-α, and ALP. These findings suggest that Z-VA has promising anti-osteoporotic properties, promoting bone formation and inhibiting bone loss. Nonetheless, further studies are warranted to clarify its underlying mechanisms and optimize its therapeutic use.