PMID- 36578051
OWN - NLM
STAT- MEDLINE
DCOM- 20221230
LR  - 20230103
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 17
IP  - 1
DP  - 2022 Dec 28
TI  - TSG-6 inhibits IL-1beta-induced inflammatory responses and extracellular matrix 
      degradation in nucleus pulposus cells by activating the PI3K/Akt signaling 
      pathway.
PG  - 572
LID - 10.1186/s13018-022-03468-9 [doi]
LID - 572
AB  - PURPOSE: Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), a secreted 
      protein associated with inflammation, is believed to possess momentous and 
      multiple anti-inflammatory and tissue-protective properties. However, the role 
      and potential mechanism of TSG-6 in cervical disk degeneration (CDD) are still 
      not clear. Hence, we aimed to explore the effect of TSG-6 on CDD. METHODS: 
      Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or 
      enzyme-linked immunosorbent assay was applied to detect the expression level of 
      TSG-6 and IL-1beta in normal and degenerated nucleus pulposus (NP) tissues. Then, 
      qRT-PCR and western blot were adopted to test the TSG-6 protein expression after 
      IL-1beta treatment (10 ng/mL) in human NP cells (HNPCs). After over-expressing 
      TSG-6, qRT-PCR was also utilized to evaluate the expression of TNF-alpha, IL-8, and 
      IL-6 and the synthesis of sulfated glycosaminoglycans (sGAGs), western blot to 
      check the expression of extracellular matrix (ECM) proteins [collagen II, 
      aggrecan, and matrix metalloproteinase-3 (MMP-3)], pain-related molecules (CGRP, 
      calcitonin gene-related peptide; NGF, nerve growth factor; SP, substance P), and 
      PI3K/Akt signaling pathway-related proteins. RESULTS: Briefly speaking, TSG-6 and 
      IL-1beta expression levels were significantly increased in CDD patient tissues; and 
      IL-1beta treatment could significantly increase TSG-6 expression in HNPCs. Further 
      research revealed that, in addition to greatly promoting sGAGs synthesis, TSG-6 
      over-expression also inhibited TNF-alpha, IL-8, and IL-6 expression and ECM 
      degradation in IL-1beta-induced HNPCs. (The collagen II and aggrecan expression was 
      up-regulated and MMP-3 expression was down-regulated.) Furthermore, 
      over-expression of TSG-6 could decrease the levels of CGRP, NGF, and SP protein 
      expression and activate the PI3K/Akt signaling pathway in IL-1beta-treated HNPCs. 
      CONCLUSION: TSG-6 inhibits inflammatory responses, ECM degradation, and 
      expression of pain-related molecules in IL-1beta-induced HNPCs by activating the 
      PI3K/Akt signaling pathway.
CI  - (c) 2022. The Author(s).
FAU - Wu, Bing
AU  - Wu B
AD  - Department of Orthopedics, Institute of the Third Medical Center, PLA (People's 
      Liberation Army) General Hospital, Beijing, 100039, China.
FAU - Guo, Xiaojin
AU  - Guo X
AD  - Department of Blood Transfusion, Institute of the Third Medical Center, PLA 
      (People's Liberation Army) General Hospital, Beijing, 100039, China.
FAU - Yan, Xiujie
AU  - Yan X
AD  - Department of Orthopedics, Institute of the Third Medical Center, PLA (People's 
      Liberation Army) General Hospital, Beijing, 100039, China.
FAU - Tian, Zikai
AU  - Tian Z
AD  - Department of Orthopedics, Institute of the Third Medical Center, PLA (People's 
      Liberation Army) General Hospital, Beijing, 100039, China.
FAU - Jiang, Wei
AU  - Jiang W
AD  - Department of Anesthesiology, Institute of the Third Medical Center, PLA 
      (People's Liberation Army) General Hospital, Beijing, 100039, China. 
      jwjw1976@sina.com.
FAU - He, Xin
AU  - He X
AD  - Department of Orthopedics, Institute of the Third Medical Center, PLA (People's 
      Liberation Army) General Hospital, Beijing, 100039, China. hexin6060@163.com.
LA  - eng
PT  - Journal Article
DEP - 20221228
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - 0 (Aggrecans)
RN  - 0 (Interleukin-6)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
RN  - 0 (Interleukin-8)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Interleukin-1beta)
SB  - IM
MH  - Humans
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Nucleus Pulposus/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Nerve Growth Factor/pharmacology
MH  - Aggrecans/metabolism
MH  - Interleukin-6/metabolism
MH  - Calcitonin Gene-Related Peptide/metabolism/pharmacology
MH  - Interleukin-8/metabolism/pharmacology
MH  - Signal Transduction
MH  - *Intervertebral Disc Degeneration/pathology
MH  - Extracellular Matrix Proteins/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Cells, Cultured
MH  - Interleukin-1beta/pharmacology/metabolism
PMC - PMC9798563
OTO - NOTNLM
OT  - Cervical disk degeneration (CDD)
OT  - Extracellular matrix (ECM)
OT  - Inflammatory response
OT  - PI3K/Akt signaling pathway
OT  - Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6)
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/12/29 06:00
MHDA- 2022/12/31 06:00
PMCR- 2022/12/28
CRDT- 2022/12/28 23:47
PHST- 2022/11/14 00:00 [received]
PHST- 2022/12/21 00:00 [accepted]
PHST- 2022/12/28 23:47 [entrez]
PHST- 2022/12/29 06:00 [pubmed]
PHST- 2022/12/31 06:00 [medline]
PHST- 2022/12/28 00:00 [pmc-release]
AID - 10.1186/s13018-022-03468-9 [pii]
AID - 3468 [pii]
AID - 10.1186/s13018-022-03468-9 [doi]
PST - epublish
SO  - J Orthop Surg Res. 2022 Dec 28;17(1):572. doi: 10.1186/s13018-022-03468-9.