Yafei Wang,Huimin Liu,Jianmin Wu,Yunjian Liao,Daifeng Lu,Feng Dong,Hongxi Li,Zhitao Zhang,Yongyun Lian
Periprosthetic osteolysis (PIO) caused by wear particles is the main cause of implant failure, which is regulated by nuclear factor κ B receptor activator ligand (RANKL)/osteoprotegerin (OPG) system. At present, there is a lack of effective drugs to prevent or treat PIO. Previous studies have confirmed that DNA methylation is closely related to postmenopausal osteoporosis and can affect the expression of OPG and RANKL . However, the relationship between DNA methylation and PIO is not clear. In this study, we investigated the inhibitory effect of 5-Aza-2-deoxycytidine (AzadC) on osteolysis induced by titanium particles in a mouse model. This inhibition mechanism is achieved by changing the ratio of RANKL/OPG in the osteolysis model. In conclusion, there is a relationship between DNA methylation and PIO. AzadC has a certain inhibitory effect on osteolysis induced by titanium particles. Regulating DNA methylation may be a new way to treat PIO. Our findings lay a foundation for epigenetic understanding and intervention of osteolysis.
Background Aseptic loosening around the prosthesis is a common cause of failure in total joint arthroplasty. Polyethylene wear particles trigger the release of inflammatory factors by macrophages. Key mediators involved in osteoclastogenesis include interleukin-6, tumor necrosis factor-α, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and bone protection hormone (Osteoprotegerin [OPG]). The purpose of our experiment was to see whether melittin can slow down the release of inflammatory mediators through the NF-kB pathway, regulate the RANKL/OPG ratio, reduce osteoclast formation, and delay the onset of arthritis in rats. Methods A total of 20 male Sprague-Dawley rats (10 months, Specific Pathogen Free, 350 g ± 20 g) were randomly divided into 5 groups: sham group, model group, melittin concentration 1 group (0.2 mg/kg), concentration 2 group (0.4 mg/kg), and concentration 3 group (0.6 mg/kg). All rats were implanted with TA2 high-purity titanium rods. A drill was used to create a bone canal along the long axis of the femur in the intercondylar notch. The model group and experimental groups were exposed to polyethylene particles, while the sham group did not receive any particles. Results The melittin group exhibited significantly increased serum levels of serum P, calcium-phosphorus product, OPG, PINP, PINP/CTX-I, and OPG/RANKKL ( P < .05). In the experimental group, micro computed tomography scanning results revealed a decrease in the amount of bone defect around the prosthesis. Immunofluorescence analysis demonstrated a decrease in the expression of IKKα and P65, while the expression of OPG showed an upward trend. Both Hematoxylin-Eosin and Tartrate-Resistant Acid Phosphatase staining revealed less osteoclast and inflammatory cell infiltration in bone resorption pits. Conclusions Our study demonstrates that melittin has the ability to inhibit the NF-kB pathway in a rat model, and reduce the impact of RANKL/OPG, thereby delaying osteoclast activity and alleviating periprosthetic osteolysis.
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