Rhoifolin ameliorates titanium particle‐stimulated osteolysis and attenuates osteoclastogenesis via RANKL‐induced NF‐κB and MAPK pathways

Abstract

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.

Inhibitory effects of biochanin A on titanium particle‐induced osteoclast activation and inflammatory bone resorption via NF‐κB and MAPK pathways

“…As the only cell with bone resorption function in the human body, OCs can lead to imbalanced bone remodelling when overactivated (Liu et al, 2019). The expression of genes related to bone‐resorptive function, such as Atpvod2, Ctr, Ctsk, and Acp5, significantly increases during OC formation (Liao et al, 2019). Therefore, one of the aims of antiosteolytic therapy is to decrease the number of OCs and subsequent bone resorption.…”

Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice

“…An increasing amount of evidence indicates that activation of the MAPK pathway, containing three major family members (ERKs, JNKs, and p38), plays a significant role in RANKL-stimulated osteoclast differentiation and formation ( Tanaka et al., 2006 ; Liao et al., 2019 ). ERK is vital for the survival of osteoclast, and JNK and p38 are also crucial for the differentiation and function of osteoclast ( Lee et al., 2002 ; Koga et al., 2019 ).…”

Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies

“…Rhoifolin, with the molecular formula C 27 H 30 O 14 , is one of the most common flavonoids and is used extensively in preclinical investigations to explore its pharmacological effects in a wide range of chronic diseases including diabetes and obesity. It is found in several citrus fruits such as bitter oranges, grapefruits, lemons, and unripe grapes [ 47 , 48 ]. Previous studies found that rhoifolin influenced several biological activities, with antioxidant [ 49 ], anti-inflammatory [ 50 ], hepatoprotective [ 51 ], and anticancer potential [ 52 ].…”