Ferulic acid-Cu(II) and Zn(II) complexes promote bone formation

Abstract The current study aims to synthesize and investigate the effects of Ferulic acid-copper(II) (FA-Cu) and Ferulic acid-Zinc(II) (FA-Zn) complexes on bone formation. The initial biocompatibility test and ALP activity assay showed that the FA-Cu and FA-Zn complexes have reached the optimum concentrations of 40 μM. An in-vitro, cellular level evaluation showed that these complexes promote the ALP activity and calcium deposition in osteoblasts. At the molecular level analysis, these complexes increased the osteoblast specific markers, Runx2 and type 1 collagen mRNAs and secretory protein levels of osteocalcin (OC) and osteonectin (ON). Also, the expression of the co-activator of osteoblast differentiation, TAZ increased and the effect of these complexes decreased the co-suppressor HDAC4. We tested the bone forming effect of these complexes in (1) zebrafish embryo bone development, (2) osteoblast distribution in scale, and (3) tail fracture models. FA-Cu and FA-Zn complex exposures have enhanced bone mineralization in zebrafish embryos' development, increased osteoblast distribution in adult zebrafish scales, and reinforced bone healing by increasing ossification at the injury site. In summary, our findings have shown that FA stimulates bone formation, and the complexes of FA-Cu and FA-Zn have further improved it.