It is commonly accepted that silicon-doped hydroxyapatite (HAp) can achieve good repair effects for both spinal fusion and bone defect filling. However, the underlying mechanism by which silicon aids such beneficial effects is still not fully understood. Herein, we report on silicon-doped hydroxyapatites with excellent biocompatibility to osteoblast cells and suggest the signaling pathway involved. Non-doped HAp and trace Si-doped HAp (Si/HAp) with Si concentration close to and higher than natural bones were synthesized (i.e., 32, 260, and 2000 ppm Si). The composition, crystal lattice vibration pattern, and morphology of these samples are characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), and SEM, respectively. Positive biological activities of these Si-doped HAp materials were demonstrated through a cytotoxicity study and with the MTT and alkaline phosphatase (ALP) activity assays. The Si-doped samples were not toxic to MC3T3-E1 cells. Indeed, osteoblast proliferation measurement illustrated that 2000 ppm Si-doped HAp increased osteoblast proliferation by about 1.6 times compared to non-doped HAp. The ALP assay also proves that the trace Si doping has the function to enhance cell proliferation and differentiation. The ALP assay showed that Si doping also enhanced cell differentiation. QRT-PCR results revealed that Si-doped HAp enhanced osteogenic differentiation of osteoblast cells by upregulating genes such as MAPK3, Fzd1, Wnt1, Lrp6, and BMP2. In conclusion, Si-doped HAp promotes osteoblast proliferation and differentiation by activating the Wnt/β-catenin and MAPK signaling pathways. This work could provide useful information of the beneficial effects of silicon in human bones and provide clues as to the molecular mechanism of the promotive effect of Si-doped HAp biomaterials.
Keywords: Hydroxyapatite; Si; Signaling pathway; Trace element.