Effects and mechanisms of natural plant active compounds for the treatment of osteoclast-mediated bone destructive diseases

Abstract

Bone-destructive diseases, caused by overdifferentiation of osteoclasts, reduce bone mass and quality, and disrupt bone microstructure, thereby causes osteoporosis, Paget’s disease, osteolytic bone metastases, and rheumatoid arthritis. Osteoclasts, the only multinucleated cells with bone resorption function, are derived from haematopoietic progenitors of the monocyte/macrophage lineage. The regulation of osteoclast differentiation is considered an effective target for the treatment of bone-destructive diseases. Natural plant-derived products have received increasing attention in recent years due to their good safety profile, the preference of natural compounds over synthetic drugs, and their potential therapeutic and preventive activity against osteoclast-mediated bone-destructive diseases. In this study, we reviewed the research progress of the potential antiosteoclast active compounds extracted from medicinal plants and their molecular mechanisms. Active compounds from natural plants that inhibit osteoclast differentiation and functions include flavonoids, terpenoids, quinones, glucosides, polyphenols, alkaloids, coumarins, lignans, and limonoids. They inhibit bone destruction by downregulating the expression of osteoclast-specific marker genes (CTSK, MMP-9, TRAP, OSCAR, DC-STAMP, V-ATPase d2, and integrin av3) and transcription factors (c-Fos, NFATc1, and c-Src), prevent the effects of local factors (ROS, LPS, and NO), and suppress the activation of various signalling pathways (MAPK, NF-κB, Akt, and Ca²⁺). Therefore, osteoclast-targeting natural products are of great value in the prevention and treatment of bone destructive diseases.

Keywords:

• Bone metabolism
• bone destructive diseases
• osteoclast
• osteoclastogenesis
• natural products

Acknowledgements

We thank the Institute of The First Affiliated Hospital of Nanchang University, Nanchang for their support of this work.

Author contributions

Xuqiang Liu and Qi Lai developed the study design. Qiang Xu, Zhiyou Cao, and Jiaqiang Xu performed the experiment, data analysis, and writing the manuscript. Min Dai and Bin Zhang analysed and interpreted the data. All authors read and approved the final manuscript.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The datasets used and analysed in the study are available on request to the corresponding author.

Additional information

Funding

This research was supported by grants from National Natural Science Foundation of China [Grant Nos. 81860404 and 81860405].