Carnosol suppresses RANKL‐induced osteoclastogenesis and attenuates titanium particles‐induced osteolysis

Abstract

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has antiinflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca 2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

“…In this present study, we found that both early phage and late phage of osteoclastogenesis were inhibited by PL. As reported in similar research works [ 31 , 32 , 33 , 34 ], we mainly revealed the compound’s molecular mechanism of action on early differentiation of osteoclasts. We, firstly, explored the effect of PL on RANKL-induced MAPK pathways [ 35 ].…”

Effects of Artemisia annua L. Essential Oil on Osteoclast Differentiation and Function Induced by RANKL

“…NFATc1 was lower in the 1 : 4000 group than in the 1 : 5000 and 1 : 6000 groups ( Figure 4(b) ). Phosphorylation of extracellular signal-regulated kinase (ERK) and p38 in the MAPK subfamily can promote osteoclast differentiation and prolong survival time [ 20 ]. The amount of p-p38 protein decreased significantly after AEO intervention at 1 : 4000 than in the control group.…”

Curcumenol mitigates chondrocyte inflammation by inhibiting the NF‑κB and MAPK pathways, and ameliorates DMM‑induced OA in mice

“…Non-steroidal anti-inflammatory drugs, and some analgesics, are the conventional medicines used to manage OA (27,28), but the side-effects of these drugs, such as hepatic damage and gastrointestinal injury, are concerns for their long-term usage (29). due their reduced side-effects, abundant production capacities and anti-inflammatory functions, plant-derived traditional medicines have gained increasing attention in previous years (30)(31)(32). Therefore, the present study investigated whether traditional medicines could be used to ameliorate the symptoms and slow the progression of OA.…”