PMID- 30953645
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20190624
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 228
DP  - 2019 Jul 1
TI  - Toll-like receptor 4 promotes high glucose-induced catabolic and inflammatory 
      responses in chondrocytes in an NF-kappaB-dependent manner.
PG  - 258-265
LID - S0024-3205(19)30261-9 [pii]
LID - 10.1016/j.lfs.2019.04.011 [doi]
AB  - Diabetes is an independent risk factor for knee osteoarthritis (OA), and 
      hyperglycaemia-induced inflammation is considered to play an important role in 
      their connection. The Toll-like receptor 4 (TLR4) regulates inflammatory 
      responses in several pathological conditions including diabetes and OA. However, 
      its role in diabetes-associated OA is poorly understood. In this study, we found 
      that TLR4 expression was higher in OA cartilage from patients with type 2 
      diabetes mellitus (T2DM) than that from non-T2DM patients. Similarly, its 
      expression was induced in primary mouse chondrocytes treated with high glucose, 
      which suggests that TLR4 upregulation in T2DM-associated OA cartilage may 
      originate from hyperglycaemia stimulation. We further discovered that TLR4 
      promoted high glucose-induced catabolic and inflammatory responses in 
      chondrocytes, and mechanistically, these effects could be explained by the 
      exacerbated activation of the transcription factor nuclear factor kappa B (NF-kappaB) 
      pathway, since its inhibition by Bay 11-7082 abrogated TLR4 effects on high 
      glucose-treated chondrocytes. Taken together, these findings may reveal a 
      promotive role of TLR4 in regulating hyperglycaemia-induced catabolism and 
      inflammation in T2DM-associated OA, and also implicate that TLR4 inhibition might 
      be of therapeutic significance in treating T2DM-associated OA.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Liang, Hongzhi
AU  - Liang H
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong 510630, China; Department of Bone and Joint 
      Surgery, Zhoukou City Central Hospital, Zhoukou, Henan 466000, China.
FAU - Wang, Huajun
AU  - Wang H
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong 510630, China.
FAU - Luo, Leifeng
AU  - Luo L
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Fan, Shuxin
AU  - Fan S
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Zhou, Li
AU  - Zhou L
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Liu, Zhaoshu
AU  - Liu Z
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Yao, Shujun
AU  - Yao S
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Zhong, Kaihua
AU  - Zhong K
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Zhao, Hancheng
AU  - Zhao H
AD  - Department of Bone and Joint Surgery, Zhoukou City Central Hospital, Zhoukou, 
      Henan 466000, China.
FAU - Zha, Zhengang
AU  - Zha Z
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan 
      University, Guangzhou, Guangdong 510630, China. Electronic address: 
      zhzgg613@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190404
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chondrocytes/*immunology/pathology
MH  - Diabetes Mellitus, Type 2/complications/*immunology/pathology
MH  - Glucose/*immunology
MH  - Humans
MH  - Inflammation/complications/immunology/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/*immunology
MH  - Osteoarthritis/complications/*immunology/pathology
MH  - Toll-Like Receptor 4/*immunology
OTO - NOTNLM
OT  - Catabolism
OT  - High glucose
OT  - Inflammation
OT  - Osteoarthritis
OT  - Toll-like receptor 4
OT  - Type 2 diabetes
EDAT- 2019/04/07 06:00
MHDA- 2019/06/25 06:00
CRDT- 2019/04/07 06:00
PHST- 2019/02/09 00:00 [received]
PHST- 2019/03/30 00:00 [revised]
PHST- 2019/04/03 00:00 [accepted]
PHST- 2019/04/07 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2019/04/07 06:00 [entrez]
AID - S0024-3205(19)30261-9 [pii]
AID - 10.1016/j.lfs.2019.04.011 [doi]
PST - ppublish
SO  - Life Sci. 2019 Jul 1;228:258-265. doi: 10.1016/j.lfs.2019.04.011. Epub 2019 Apr 
      4.