Antioxidative fullerol prevents bone loss due to its anti-osteoclastogenic and pro-osteogenic activities

Abstract

Purpose

Previous studies have demonstrated a role for oxidative stress in promoting osteoclastogenesis and bone loss. This study aimed to assess the ability of fullerol, a powerful nano-antioxidant, to prevent bone loss and promote osteogenesis, and additionally provide novel insight into mechanisms of action.

Methods

Osteoclastogenesis assays were conducted in murine progenitor cells stimulated with receptor activator of nuclear factor kappa-B ligand (RANKL), with and without fullerol. The cells were stained to detect the presence of osteoclastic markers and RT-PCR was used to measure the expression of osteoclastic genes. To assess osteogenesis, stem cells were incubated in osteogenic medium with or without fullerol, as well as with an inhibitor of p38-MAPK, then stained to determine mineralization. RT-PCR was used to measure osteoblastic gene expression. In the animal model, rabbits were injected with methylprednisolone with or without fullerol, or a control. Animals were later euthanized and spine fragments underwent imaging assessment.

Results

Fullerol prevented formation of osteoclasts in RAW264.7 cells exposed to RANKL as well as the expression of osteoclastic genes TRAP, CATK, and MMP9. D1 cells exposed to fullerol displayed an increase in extracellular matrix mineralization and expression of osteoblastic genes. However, when fullerol was added in the presence of a p38-MAPK inhibitor, its effects on mineralization were attenuated. In a rabbit model of steroid-induced osteoporosis, simultaneous injection of fullerol reduced vertebral bone loss, decreased trabecular separation, and increased trabecular number.

Conclusion

Fullerol shows early potential for use in osteoporosis therapy, due to its ability to inhibit osteoclast formation and stimulate osteogenesis.