2023, Vol. 27 ›› Issue (2): 293-299

Receptor activator of nuclear factor-kappa B ligand signal transduction mechanism and osteoclast activation

Chen Feng1, Ren Guowu1, Zhang Xiaoyun2, Chen Yueping2, Shi Rusheng1   

Abstract: BACKGROUND: Osteoclasts are the only known type of bone resorption cells, and its life activities are essential to the normal development of bones and the repair of bone damage. Osteoclasts show abnormal proliferation and differentiation and increased bone resorption activity in most bone diseases, while receptor activator of nuclear factor-kappa B (RANK) is a key signal pathway that regulates osteoclastogenesis.
OBJECTIVE: To summarize the latest research progress on the downstream targets of osteoclast RANK signal and DNA transcription factors at home and abroad, and provide a basis for the research and treatment of related diseases.
METHODS: A computer-based retrieval was conducted in CNKI, WanFang, VIP, PubMed, Embase and Web of Science databases. The search terms were “osteoclasts, osteoclast precursor cells, osteoporosis, bone metabolism, pathogenesis, epigenetics, signaling pathway, signal transduction, transcription factors, tissue engineering” in Chinese and English. The retrieval time was set to 2017-2021. Finally 52 articles were included according to the inclusion and exclusion criteria.
RESULTS AND CONCLUSION: The special structure of RANK determines that its signal transduction needs to be combined with tumor necrosis factor receptor-associated factor 6 to recruit a variety of proteins, active enzymes and cytokines to form a RANK complex with intrinsic enzyme activity. This complex then activates nuclear factor-κB, mitogen-activated protein kinase and other signal pathways, ultimately regulating osteoclast differentiation, proliferation, and bone resorption.
Key words: osteoclast, receptor activator of nuclear factor-kappa B, cell signal pathway, osteoporosis, bone tissue engineering, review