PMID- 34056329
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210601
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 6
IP  - 17
DP  - 2021 May 4
TI  - Telmisartan Mitigates TNF-alpha-Induced Type II Collagen Reduction by Upregulating 
      SOX-9.
PG  - 11756-11761
LID - 10.1021/acsomega.1c01170 [doi]
AB  - The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)-induced degradation 
      of extracellular matrix (ECM), such as type II collagen in chondrocytes, plays an 
      important role in the development of osteoarthritis (OA). Telmisartan, an 
      angiotensin II (Ang-II) receptor blocker, is a licensed drug used for the 
      treatment of hypertension. However, the effects of Telmisartan in tumor necrosis 
      factor-alpha (TNF-alpha)-induced damage to chondrocytes and the progression of OA are 
      unknown. In this study, we found that treatment with Telmisartan attenuated 
      TNF-alpha-induced oxidative stress by reducing the levels of mitochondrial reactive 
      oxygen species (ROS) and the production of protein carbonyl in human C28/I2 
      chondrocytes. Interestingly, Telmisartan inhibited TNF-alpha-induced expression and 
      secretions of proinflammatory mediators such as interleukin-1beta (IL-1beta), 
      interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). Notably, 
      stimulation with TNF-alpha reduced the levels of type II collagen at both the mRNA 
      and the protein levels, which was rescued by the treatment with Telmisartan. 
      Mechanistically, we found that Telmisartan restored TNF-alpha-induced reduction of 
      SOX-9. Silencing of SOX-9 blocked the inhibitory effects of Telmisartan against 
      TNF-alpha-induced degradation of type II collagen. These findings suggest that 
      Telmisartan might be a potential and promising agent for the treatment of OA.
CI  - (c) 2021 The Authors. Published by American Chemical Society.
FAU - Zhang, Xiuying
AU  - Zhang X
AD  - Department of Rheumatology and Immunology, Zibo Central Hospital, Zibo 255036, 
      China.
FAU - Dong, Yanfeng
AU  - Dong Y
AD  - Department of Cardiology, Zhangdian District peopleundefineds Hospital, Zibo 
      255036, China.
FAU - Dong, Hanyu
AU  - Dong H
AD  - Department of Endocrinology, Zibo Maternal and Child Health Hospital, Zibo 
      255036, China.
FAU - Cui, Yanhui
AU  - Cui Y
AD  - Department of Rheumatology and Immunology, Zibo Central Hospital, Zibo 255036, 
      China.
FAU - Du, Qing
AU  - Du Q
AD  - Department of Rheumatology and Immunology, Zibo Central Hospital, Zibo 255036, 
      China.
FAU - Wang, Xiaoli
AU  - Wang X
AD  - Department of Rheumatology and Immunology, Zibo Central Hospital, Zibo 255036, 
      China.
FAU - Li, Lanlan
AU  - Li L
AD  - Department of Rheumatology and Immunology, Zibo Central Hospital, Zibo 255036, 
      China.
FAU - Zhang, Hongju
AU  - Zhang H
AUID- ORCID: 0000-0002-9749-9308
AD  - Department of Rheumatology and Immunology, Zibo Central Hospital, Zibo 255036, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210422
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC8154015
COIS- The authors declare no competing financial interest.
EDAT- 2021/06/01 06:00
MHDA- 2021/06/01 06:01
PMCR- 2021/04/22
CRDT- 2021/05/31 06:22
PHST- 2021/03/04 00:00 [received]
PHST- 2021/04/09 00:00 [accepted]
PHST- 2021/05/31 06:22 [entrez]
PHST- 2021/06/01 06:00 [pubmed]
PHST- 2021/06/01 06:01 [medline]
PHST- 2021/04/22 00:00 [pmc-release]
AID - 10.1021/acsomega.1c01170 [doi]
PST - epublish
SO  - ACS Omega. 2021 Apr 22;6(17):11756-11761. doi: 10.1021/acsomega.1c01170. 
      eCollection 2021 May 4.