carnosol and Osteolysis

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 anti-inflammatory, 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

Topics: Abietanes; Animals; Bone Resorption; Calcium Signaling; Female; Gene Expression Regulation; Male; MAP Kinase Signaling System; Mice, Inbred C57BL; Models, Biological; NF-kappa B; NF-KappaB Inhibitor alpha; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteolysis; Proteolysis; RANK Ligand; Skull; Titanium

Osteolysis is characterized by the imbalance of bone remodeling triggered by excessive activation of osteoclasts, which ultimately leads to pathological bone destruction. Diseases caused by overactive osteoclasts, such as osteolysis around the prosthesis, periodontitis and osteoporosis, are clinically common but lack effective treatment. Therefore, exploring regimens that could specifically impair the formation and function of osteoclasts has become a breakthrough in the treatment of these diseases. Carnosol is a natural phenolic diterpene with anti-inflammatory, antibacterial, anti-tumor and antioxidant properties. In this study, we found that carnosol can impede RANKL-induced osteoclastogenesis via modulating the activation of NF-κb and JNK signaling pathways in vitro. Additionally, we confirmed that carnosol could alleviate bone loss in amurine model of LPS-induced inflammatory bone erosion in vivo. Thence, these findings demonstrate that carnosol may be a potentially effective regent for the treatment of osteoclast-related disorders.

Topics: Abietanes; Animals; Anti-Inflammatory Agents; Bone Remodeling; Disease Models, Animal; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoclasts; Osteogenesis; Osteolysis; Phosphorylation; RANK Ligand; RAW 264.7 Cells; Signal Transduction