Role and Regulation of Transcription Factors in Osteoclastogenesis

Abstract

Bones serve mechanical and defensive functions, as well as regulating the balance of calcium ions and housing bone marrow.. The qualities of bones do not remain constant. Instead, they fluctuate throughout life, with functions increasing in some situations while deteriorating in others. The synchronization of osteoblast-mediated bone formation and osteoclast-mediated bone resorption is critical for maintaining bone mass and microstructure integrity in a steady state. This equilibrium, however, can be disrupted by a variety of bone pathologies. Excessive osteoclast differentiation can result in osteoporosis, Paget's disease, osteolytic bone metastases, and rheumatoid arthritis, all of which can adversely affect people's health. Osteoclast differentiation is regulated by transcription factors NFATc1, MITF, C/EBPα, PU.1, NF-κB, and c-Fos. The transcriptional activity of osteoclasts is largely influenced by developmental and environmental signals with the involvement of co-factors, RNAs, epigenetics, systemic factors, and the microenvironment. In this paper, we review these themes in regard to transcriptional regulation in osteoclastogenesis.

Keywords: epigenetics; osteoclast; osteoclast differentiation; osteoclastogenesis; transcription factor.

Figure 2

Intercellular communication between osteoclasts and osteoblasts, osteocytes, and adipocytes.

Figure 3

Intercellular communication between osteoclasts and immune cells.

Figure 1

Differentiation pathway of osteoclastogenesis. M-CFU, myeloid colony-forming units; MPPs, multipotent progenitors; CMPs, common myeloid progenitors; CLPs, common lymphoid progenitors; MEPs, megakaryocyte/erythrocyte progenitors; MODPs, macrophage/osteoclast/dendritic cell progenitors.

Figure 4

Osteoclastogenic pathway consisting of major transcription factors of osteoclasts.