ThPOK Inhibits Osteoclast Formation Via NFATc1 Transcription and Function

Wei Zou, Takashi Izawa, Nidhi Rohatgi, Steven Y. Zou, Yongjia Li, Steven L. Teitelbaum

Research output: Contribution to journalArticlepeer-review

Abstract

Both LRF (Zbtb7a) and ThPOK (Zbtb7b) belong to the POK (BTB/POZ and Kruppel) family of transcription repressors that participate in development, differentiation, and oncogenesis. Although LRF mediates osteoclast differentiation by regulating NFATc1 expression, the principal established function of ThPOK is transcriptional control of T-cell lineage commitment. Whether ThPOK affects osteoclast formation or function is not known. We find that marrow macrophage ThPOK expression diminishes with exposure to receptor activator of NF-kB ligand (RANKL), but ThPOK deficiency does not affect osteoclast differentiation. On the other hand, enhanced ThPOK, in macrophages, substantially impairs osteoclastogenesis. Excess ThPOK binds the NFATc1 promoter and suppresses its transcription, suggesting a mechanism for its osteoclast inhibitory effect. Despite suppression of osteoclastogenesis by excess ThPOK being associated with diminished NFATc1, osteoclast formation is not rescued by NFATc1 overexpression. Thus, ThPOK appears to inhibit NFATc1 transcription and its osteoclastogenic capacity, while its depletion has no effect on the bone-resorptive cell.

Original languageEnglish
Article numbere10613
JournalJBMR Plus
Volume6
Issue number4
DOIs
Publication statusPublished - Apr 2022

Keywords

  • CELL/TISSUE SIGNALING
  • CELLS OF BONE
  • DISEASES AND DISORDERS OF/RELATED TO BONE
  • OSTEOCLASTS
  • OSTEOPOROSIS
  • TRANSCRIPTION FACTORS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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