The efficacy and potential mechanism of cnidium lactone to inhibit osteoclast differentiation

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 47; no. 1; pp. 3087 - 3093
• Main Authors: Liang, Jun-Yang, Wu, Wen-Liang, Chen, Yun-Xia, Liu, Haichun
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2019; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Biomedical materials; Bone growth; Bone mass; Bone Resorption - drug therapy; c-Fos protein; Cattle; Cell Differentiation - drug effects; Cell Survival - drug effects; Cnidium; Cnidium - chemistry; Cnidium lactone; Differentiation; Gene expression; Gene Expression Regulation - drug effects; Lactones - pharmacology; Lactones - therapeutic use; MAP kinase; Mice; Molecular modelling; NF-κB protein; NFATC Transcription Factors - metabolism; osteoclast; Osteoclastogenesis; Osteoclasts; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoporosis; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinases - metabolism; PI3K-Akt signalling pathway; Pretreatment; Proto-Oncogene Proteins c-fos - metabolism; RAW 264.7 Cells; Signal transduction; Signal Transduction - drug effects; Signaling; TRANCE protein; PI3K-Akt signalling pathway; Cnidium lactone; differentiation; osteoclast
• ISSN: 2169-1401; 2169-141X
• DOI: 10.1080/21691401.2019.1637881

Cnidium lactone is effective in the maintenance of bone mass in various osteoporosis models; however, the precise molecular mechanisms are not understood. In this study, we investigated the effects and underlying mechanisms of action of cnidium lactone on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Cnidium lactone dose-dependently inhibited osteoclast differentiation and formation, decreased the bone-resorbing activity of osteoclasts, and downregulated the expression of osteoclast differentiation marker genes. Cnidium lactone treatment considerably reduced RANKL-induced p38 MAPK and PI3K-Akt signal activity in RAW264.7 cells. The cnidium lactone-induced osteoclastogenesis was significantly attenuated by inhibition of p38 and PI3K through pretreatment with SB203580 and LY294002, respectively. Furthermore, cnidium lactone inhibited the expression of c-Fos and NFATc-1 with dose-dependently and enhanced by SB203580 and LY294002. In conclusion, cnidium lactone inhibits osteoclast differentiation through p38 MAPK and PI3K-Akt signalling pathway/c-Fos/NFATc1 signalling pathway.