Strategy to inhibit effective differentiation of RANKL-induced osteoclasts using vitamin D-conjugated gold nanoparticles

摘要

Osteoporosis, a major skeletal disorder, is an increasing worldwide social burden among the aging society, which develops when the ratio of bone resorption regulated by osteoclasts reverses the bone formation in the bone remodeling cycle. Basically, osteoporosis is commonly treated using bone resorption inhibitors such as bisphosphonates. However, long-term intake of bisphosphonates exposes patients to traumatic side effects such as digestive disorders and medication-related osteonecrosis of the jaw (MRONJ). Therefore, an alternative solution is required in the area of bone tissue engineering. Hence, to solve this issue, in this study, we designed GNPs and functionalized GNPs' surface through conjugation with SH-PEG-vitamin D (SPVD) via the Au-S binding system. Vitamin D-conjugated GNPs (VGNPs) were successfully synthesized and confirmed by various physicochemical analyses. These conjugated nanoparticles significantly increased cell viability and decreased tartrate-resistant acid phosphatase (TRAP) activity and actin ring formation. In addition, VGNPs suppressed the expression of genes associated with osteoclast differentiation. Finally, VGNPs also significantly inhibited the expression of reactive oxygen species (ROS). These results demonstrate the inhibitory effect of VGNPs on osteoclast differentiation and suggest that the developed nanocarriers could play a key role as a bone resorption inhibitor in the field of bone tissue engineering.