Prosthesis loosening is a highly troublesome clinical problem following total joint arthroplasty. Wear‐particle‐induced osteoclastogenesis has been shown to be the primary cause of periprosthetic osteolysis that eventually leads to aseptic prosthesis loosening. Therefore, inhibiting osteoclastogenesis is a promising strategy to control periprosthetic osteolysis. The possible mechanism of action of rhoifolin on osteoclastogenesis and titanium particle‐induced calvarial osteolysis was examined in this study. The in vitro study showed that rhoifolin could strongly suppress the receptor activators of nuclear factor‐κB (NF‐κB) ligand‐stimulated osteoclastogenesis, hydroxyapatite resorption, F‐actin formation, and the gene expression of osteoclast‐related genes. Western blot analysis illustrated that rhoifolin could attenuate the NF‐κB and mitogen‐activated protein kinase pathways, and the expression of transcriptional factors nuclear factor of activated T cells 1 (NFATc1) and c‐Fos. Further studies indicated that rhoifolin inhibited p65 translocation to the nucleus and the activity of NFATc1 and NF‐κB rhoifolin could decrease the number of tartrate‐resistant acid phosphate‐positive osteoclasts and titanium particle‐induced C57 mouse calvarial bone loss in vivo. In conclusion, our results suggest that rhoifolin can ameliorate the osteoclasts‐stimulated osteolysis, and may be a potential agent for the treatment of prosthesis loosening.

Revision operations have become a new issue after successful artificial joint replacements, and periprosthetic osteolysis leading to prosthetic loosening is the main cause of why the overactivation of osteoclasts (OCs) plays an important role. The effect of biochanin A (BCA) has been examined in osteoporosis, but no study on the role of BCA in prosthetic loosening osteolysis has been conducted yet. In this study, we utilised enzyme-linked immunosorbent assay, computed tomography imaging, and histological analysis. Results showed that BCA downregulated the secretion levels of tumor necrosis factor-α, interleukin-1α (IL-1α), and IL-1β to suppress inflammatory responses. The secretion levels of receptor-activated nuclear factor-κB ligand, CTX-1, and osteoclast-associated receptor as well as Ti-induced osteolysis were also reduced. BCA effectively inhibited osteoclastogenesis and suppressed hydroxyapatite resorption by downregulating OC-related genes in vitro. Analysis of mechanisms indicated that BCA inhibited the signalling pathways of mitogenactivated protein kinase (P38, extracellular signal-regulated kinase, and c-JUN N-terminal kinase) and nuclear factor-κB (inhibitor κB-α and P65), thereby downregulating the expression of nuclear factor of activated T cell 1 and c-Fos. In conclusion, BCA may be an alternative choice for the prevention of prosthetic loosening caused by OCs.

Wearing titanium particle‐induced osteoclastogenesis, accompanied by peri‐implant osteolysis, is the main cause of long‐term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri‐implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti‐inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle‐induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL‐induced osteoclastogenesis, fusion of F‐actin rings, bone resorption, and expression of osteoclast marker genes in a dose‐dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL‐induced osteoclastogenesis via the inhibition of NF‐κB and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c‐Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle‐induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri‐implant osteolysis.