PMID- 34779501
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20220221
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 25
IP  - 1
DP  - 2022 Jan
TI  - Tetramethylpyrazine alleviates endoplasmic reticulum stress‑activated apoptosis 
      and related inflammation in chondrocytes.
LID - 12 [pii]
LID - 10.3892/mmr.2021.12528 [doi]
AB  - Excessive apoptosis of chondrocytes and degradation of the extracellular matrix 
      (ECM) contribute to the typical pathological characteristics of osteoarthritis 
      (OA). Various studies have reported that tetramethylpyrazine (TMP) protects 
      against multiple disorders by inhibiting inflammation and oxidative stress. The 
      present study investigated the effects of TMP on chondrocytes and evaluated the 
      associated mechanisms. To determine the effect of TMP on OA and the underlying 
      mechanisms, chondrocytes were incubated with TMP and IL‑1beta or thapsigargin (TG) 
      Western blotting assays were performed to examine the expression levels of 
      endoplasmic reticulum (ER) stress proteins, and TUNEL staining, fluorescence 
      immunostaining and reverse transcription‑quantitative PCR were used to determine 
      the apoptosis levels, and catabolic and inflammatory factors. It was found that 
      TMP protected chondrocytes by suppressing IL‑1beta‑induced expression of 
      glucose‑regulated protein 78 (GRP78) and CHOP (an apoptotic protein). TMP 
      regulated the TG‑mediated upregulated expression of GRP78 and CHOP in the 
      chondrocytes of rats, as well as markedly suppressed levels of ER 
      stress‑triggered inflammatory cytokines (TNF‑alpha and IL‑6). Furthermore, TMP 
      modulated TG‑induced changes in ECM catabolic metabolism in rat chondrocytes. 
      Collectively, TMP alleviated ER‑stress‑activated apoptosis and related 
      inflammation in chondrocytes, indicating that it has therapeutic potential for 
      the treatment of OA.
FAU - Hu, Shuai
AU  - Hu S
AD  - Joint and Traumatology Department, The First Affiliated Hospital of Hainan 
      Medical University, Haikou, Hainan 570100, P.R. China.
FAU - Wang, Sheng
AU  - Wang S
AD  - Joint and Traumatology Department, The First Affiliated Hospital of Hainan 
      Medical University, Haikou, Hainan 570100, P.R. China.
FAU - He, Jie
AU  - He J
AD  - Joint and Traumatology Department, The First Affiliated Hospital of Hainan 
      Medical University, Haikou, Hainan 570100, P.R. China.
FAU - Bian, Yangyang
AU  - Bian Y
AD  - Department of Trauma Medical Center, The First Affiliated Hospital of Hainan 
      Medical University, Haikou, Hainan 570100, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20211115
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Ddit3 protein, rat)
RN  - 0 (GRP78 protein, rat)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (IL1B protein, rat)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Pyrazines)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - V80F4IA5XG (tetramethylpyrazine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Chondrocytes/*metabolism/physiology
MH  - Endoplasmic Reticulum Stress/*drug effects/physiology
MH  - Extracellular Matrix/metabolism
MH  - Gene Expression/genetics
MH  - Gene Expression Regulation/genetics
MH  - Heat-Shock Proteins/metabolism
MH  - Inflammation/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Male
MH  - Osteoarthritis/metabolism
MH  - Oxidative Stress/drug effects
MH  - Pyrazines/metabolism/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factor CHOP/metabolism
PMC - PMC8600404
OTO - NOTNLM
OT  - apoptosis
OT  - endoplasmic reticulum stress
OT  - inflammation
OT  - osteoarthritis
OT  - tetramethylpyrazine
COIS- The authors declare that they have no competing interests.
EDAT- 2021/11/16 06:00
MHDA- 2022/02/22 06:00
PMCR- 2021/11/09
CRDT- 2021/11/15 08:54
PHST- 2021/05/22 00:00 [received]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/11/15 08:54 [entrez]
PHST- 2021/11/16 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2021/11/09 00:00 [pmc-release]
AID - 12 [pii]
AID - MMR-25-01-12528 [pii]
AID - 10.3892/mmr.2021.12528 [doi]
PST - ppublish
SO  - Mol Med Rep. 2022 Jan;25(1):12. doi: 10.3892/mmr.2021.12528. Epub 2021 Nov 15.