Zou Wei, Izawa Takashi, Rohatgi Nidhi, Zou Steven Y, Li Yongjia, Teitelbaum Steven L
Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology Washington University School of Medicine St. Louis MO USA.
Department of Orthodontics Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan.
JBMR Plus. 2022 Mar 14;6(4):e10613. doi: 10.1002/jbm4.10613. eCollection 2022 Apr.
Both LRF () and ThPOK () 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. © 2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
LRF（）和ThPOK（）均属于转录抑制因子的POK（BTB/POZ和Kruppel）家族，该家族参与发育、分化和肿瘤发生过程。尽管LRF通过调节NFATc1的表达介导破骨细胞分化，但ThPOK的主要既定功能是对T细胞谱系定向的转录控制。ThPOK是否影响破骨细胞的形成或功能尚不清楚。我们发现，骨髓巨噬细胞中ThPOK的表达随着暴露于核因子-κB受体激活剂配体（RANKL）而减少，但ThPOK缺陷并不影响破骨细胞的分化。另一方面，巨噬细胞中ThPOK的增强会显著损害破骨细胞生成。过量的ThPOK与NFATc1启动子结合并抑制其转录，提示了其破骨细胞抑制作用的机制。尽管过量的ThPOK抑制破骨细胞生成与NFATc1减少有关，但NFATc1的过表达并不能挽救破骨细胞的形成。因此，ThPOK似乎抑制NFATc1转录及其破骨细胞生成能力，而其缺失对骨吸收细胞没有影响。© 2022作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
