TY - JOUR
T1 - ThPOK inhibits osteoclast formation via NFATc1 transcription and function
AU - Zou, Wei
AU - Izawa, Takashi
AU - Rohatgi, Nidhi
AU - Zou, Steven Y.
AU - Li, Yongjia
AU - Teitelbaum, Steven L.
N1 - Publisher Copyright:
This article is protected by copyright. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Both LRF (Zbtb7a) and ThPOK (Zbtb7b) belong to the POK (BTB/POZ and Kruppel) family of transcription repressors which participate in development, differentiation and oncogenesis. While 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 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. This article is protected by copyright. All rights reserved.
AB - Both LRF (Zbtb7a) and ThPOK (Zbtb7b) belong to the POK (BTB/POZ and Kruppel) family of transcription repressors which participate in development, differentiation and oncogenesis. While 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 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. This article is protected by copyright. All rights reserved.
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U2 - 10.1002/jbm4.10621
DO - 10.1002/jbm4.10621
M3 - Article
AN - SCOPUS:85146138929
SN - 2473-4039
JO - JBMR Plus
JF - JBMR Plus
ER -