The Dopamine D1 Receptor Attenuates Titanium Particle-Induced Inhibition of Osteogenesis by Activating the Wnt Signaling Pathway.

Periprosthetic osteolysis (PPO), caused by wear particles, has become a major cause of joint replacement failure. Secondary surgery after joint replacement poses a serious threat to public health worldwide. Therefore, determining how to effectively inhibit wear particle-induced PPO has become an urgent issue. Recently, the interaction between osteogenic inhibition and wear particles at the biological interface of the implant has been found to be an important factor in the pathological process. Previous studies have found that the central nervous system plays an important role in the regulation of bone formation and bone remodeling. Dopamine (DA), an important catecholamine neurotransmitter, plays an integral role in the physiological and pathological processes of various tissues through its corresponding receptors. Our current study found that upregulation of dopamine first receptors could be achieved by activating the Wnt/ß-catenin pathway, improving osteogenesis in vivo and in vitro, and significantly reducing the inhibition of titanium particle-induced osteogenesis. Overall, these findings suggest that dopamine first receptor (D1R) may be a plausible target to promote osteoblast function and resist wear particle-induced PPO.

Avicularin Alleviates Osteoporosis in Ovariectomized Mice by Inhibiting Osteoclastogenesis through NF-κB Pathway Inhibition.

Osteoporosis (OP) is mainly manifested by bone loss and bone degeneration. OP is considered a risk factor for pathological fractures, as well as impacts the health of middle-aged and elderly individuals. Drug therapy remains the main treatment scheme for OP; however, its efficacy is limited and has been associated with serious side effects. Therefore, it is important to develop new, effective, and safe treatment methods for OP. Avicularin (AL) is a flavonoid and quercetin derivative from various plants. Our study showed that AL disrupts osteoclast activation and resorptive function via inhibition of the RANKL-induced osteoclast differentiation together with the resorption capacity of bone marrow-derived macrophages (BMMs). Hence, AL prevents the activation and resorptive activity of osteoclasts. The results of qPCR showed that genes related to osteoclasts exhibited downregulated expression after AL treatment. Furthermore, AL inhibited RANKL-induced phosphorylation as well as degradation of the inhibitor IκBα of the NF-κB pathway, together with P65 phosphorylation in BMMs. We used an OP mouse model that was established by ovariectomy (OVX). Relative to untreated OP mice, mice that received AL treatment showed a significant increase in bone mineral density; however, the expression of TRAP, NFATC1, mmp9, and CTX-1 was significantly reduced. These results indicate that AL disrupts osteoclastogenesis via inhibition of the NF-κB pathway, which in turn improves OVX-induced OP.