PMID- 36821040
OWN - NLM
STAT- MEDLINE
DCOM- 20230307
LR  - 20230307
IS  - 2523-899X (Electronic)
IS  - 2523-899X (Linking)
VI  - 43
IP  - 1
DP  - 2023 Feb
TI  - Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the 
      Extracellular Matrix through Upregulation of the GATA3 Expression.
PG  - 146-155
LID - 10.1007/s11596-022-2686-1 [doi]
AB  - OBJECTIVE: Disc calcification is strongly associated with disc degeneration; 
      however, the underlying mechanisms driving its pathogenesis are poorly 
      understood. This study aimed to provide a gene expression profile of nucleus 
      pulposus cells (NPCs) from calcified discs, and clarify the potential mechanism 
      in disc degeneration. METHODS: Primary NPCs were isolated from calcified and 
      control discs (CAL-NPC and CON-NPC), respectively. The proliferation and 
      extracellular matrix (ECM) metabolism capacities of the cells were evaluated 
      using MTT and Western blotting, respectively. RNA sequencing was used to identify 
      differentially expressed genes (DEGs) in the CAL-NPCs. The biological functions 
      of the DEGs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of 
      Genes and Genomes (KEGG) databases. The transcription factor database and 
      Cytoscape software were used to construct the transcription factor-DEGs 
      regulatory network. The role of the verified transcription factor in NPC 
      proliferation and ECM metabolism was also investigated. RESULTS: The CAL-NPCs 
      exhibited a lower proliferation rate and higher ECM degradation capacity than the 
      CON-NPCs. In total, 375 DEGs were identified in the CAL-NPCs. The GO and KEGG 
      analyses showed that the DEGs were primarily involved in the regulation of 
      ribonuclease activity and NF-kappa B and p53 signaling pathways. GATA-binding 
      protein 3 (GATA3) with the highest verified levels was selected for further 
      studies. Overexpression of GATA3 in the CON-NPCs significantly inhibited their 
      proliferation and promoted their ECM degradation function, while the knockdown of 
      GATA3 in the CAL-NPCs resulted in the opposite phenotypes. CONCLUSION: This study 
      provided a comprehensive gene expression profile of the NPCs from the calcified 
      discs and supported that GATA3 could be a potential target for reversing 
      calcification-associated disc degeneration.
CI  - (c) 2023. Huazhong University of Science and Technology.
FAU - Dong, Yu-Lei
AU  - Dong YL
AD  - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Science and Peking Union Medical College, Beijing, 100730, 
      China.
FAU - Tang, Ning
AU  - Tang N
AD  - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Science and Peking Union Medical College, Beijing, 100730, 
      China.
FAU - Zhao, Hong
AU  - Zhao H
AD  - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Science and Peking Union Medical College, Beijing, 100730, 
      China.
FAU - Liang, Jin-Qian
AU  - Liang JQ
AD  - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Science and Peking Union Medical College, Beijing, 100730, 
      China. string218@126.com.
LA  - eng
PT  - Journal Article
DEP - 20230223
PL  - China
TA  - Curr Med Sci
JT  - Current medical science
JID - 101729993
RN  - 0 (NF-kappa B)
RN  - 0 (GATA3 protein, human)
RN  - 0 (GATA3 Transcription Factor)
SB  - IM
MH  - Humans
MH  - *Nucleus Pulposus/metabolism/pathology
MH  - *Intervertebral Disc Degeneration
MH  - Up-Regulation
MH  - Extracellular Matrix/metabolism/pathology
MH  - NF-kappa B/metabolism
MH  - GATA3 Transcription Factor/metabolism
OTO - NOTNLM
OT  - GATA-binding protein 3
OT  - RNA sequencing
OT  - calcified disc
OT  - disc degeneration
OT  - nucleus pulposus cells
EDAT- 2023/02/24 06:00
MHDA- 2023/03/08 06:00
CRDT- 2023/02/23 11:37
PHST- 2022/03/20 00:00 [received]
PHST- 2022/05/25 00:00 [accepted]
PHST- 2023/02/24 06:00 [pubmed]
PHST- 2023/03/08 06:00 [medline]
PHST- 2023/02/23 11:37 [entrez]
AID - 10.1007/s11596-022-2686-1 [pii]
AID - 10.1007/s11596-022-2686-1 [doi]
PST - ppublish
SO  - Curr Med Sci. 2023 Feb;43(1):146-155. doi: 10.1007/s11596-022-2686-1. Epub 2023 
      Feb 23.