Laser irradiation decreases sclerostin expression in bone and osteogenic cells.

Abstract

Anti-sclerostin monoclonal antibody romosozumab, a treatment for osteoporosis, reduced vertebral fracture risk and clinical fracture. Laser irradiation triggers various effects, including bio-stimulation, which can induce beneficial therapeutic effects and biological responses. Originally, we performed in vivo experiments to clarify the mechanism of better bone healing in laser-ablated bone. Here, we evaluated comprehensive and sequential gene expression in Er:YAG laser-ablated, bur-drilled, and nontreated control bones, and found laser irradiation suppressed Sost (coding protein: sclerostin) expression in the bone, possibly via stimulation of mechanotransducers. Surprisingly, bio-stimulation effect of laser suppressed Sost expression in the primary osteogenic cells. Decreased sclerostin expression after laser irradiation was also validated both in vivo and in vitro. In addition, sequential microarray analysis revealed that the gene expression pattern was clearly different at 24hours after bone ablation between bur-drilled and laser-ablated bones. The Hippo signaling pathway was significantly enriched, whereas inflammation-related pathways were not affected at 6hours after the laser ablation, indicating that laser irradiation caused mechanical stimulation. Only bur-drilled bone showed enriched inflammation-related gene sets and pathways at 24hours, not in the laser-ablated bone. Our study suggests that laser irradiation may become a new treatment modality for osteoporosis, by inhibiting sclerostin expression without inducing inflammation.