PMID- 34438368
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20220201
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 16
DP  - 2021 Aug 26
TI  - NLRC5 attenuates inflammatory response in IL-1beta-stimulated human osteoarthritis 
      chondrocytes through the NF-kappaB signaling pathway.
PG  - 20651-20660
LID - 10.18632/aging.203453 [doi]
AB  - NOD-like receptor family caspase recruitment domain family domain containing 5 
      (NLRC5) has been found to be a critical mediator of inflammatory response. 
      However, the role of NLRC5 in osteoarthritis (OA) has not been reported. Our 
      results showed that NLRC5 was down-regulated by IL-1beta induction in chondrocytes. 
      Overexpression of NLRC5 in chondrocytes significantly suppressed IL-1beta-induced 
      inflammatory response through inhibiting the production of multiple inflammatory 
      mediators including inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 
      (COX-2), prostaglandin E2 (PGE2), NO, TNF-alpha and IL-6, as well matrix 
      metalloproteinase 3 (MMP-3) and MMP-13. Consistently, NLRC5 knockdown exhibited 
      opposite effects on the production of these inflammatory mediators in 
      IL-1beta-induced chondrocytes. Furthermore, overexpression of NLRC5 increased the 
      IkBalpha expression, while decreased the p-p65 expression, indicating that NLRC5 
      inhibited the activation of NF-kappaB signaling. Additionally, inhibition of NF-kappaB by 
      PDTC mitigated the si-NLRC5-mediated promotion of IL-1beta-induced inflammatory 
      injury in chondrocytes. Finally, NLRC5 treatment ameliorated cartilage 
      degeneration in an OA model in rats. Taken together, these findings revealed that 
      NLRC5 attenuated IL-1beta-induced inflammatory injury in chondrocytes through 
      regulating the NF-kappaB signaling.
FAU - Mu, Yiping
AU  - Mu Y
AD  - Hand Surgery Department, Central Hospital Affiliated to Shen Yang Medical 
      Collage, Shenyang 110024, Liaoning Province, China.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Hand Surgery Department, Central Hospital Affiliated to Shen Yang Medical 
      Collage, Shenyang 110024, Liaoning Province, China.
FAU - Wu, Jie
AU  - Wu J
AD  - Hand Surgery Department, Central Hospital Affiliated to Shen Yang Medical 
      Collage, Shenyang 110024, Liaoning Province, China.
FAU - Li, Qi
AU  - Li Q
AD  - Hand Surgery Department, Central Hospital Affiliated to Shen Yang Medical 
      Collage, Shenyang 110024, Liaoning Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210826
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NLRC5 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Chondrocytes/*immunology
MH  - Cyclooxygenase 2/genetics/immunology
MH  - Dinoprostone/immunology
MH  - Humans
MH  - Interleukin-1beta/genetics/*immunology
MH  - Intracellular Signaling Peptides and Proteins/genetics/*immunology
MH  - Male
MH  - Matrix Metalloproteinase 13/genetics/immunology
MH  - NF-kappa B/genetics/*immunology
MH  - Nitric Oxide Synthase Type II/genetics/immunology
MH  - Osteoarthritis/genetics/*immunology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
PMC - PMC8436921
OTO - NOTNLM
OT  - NF-kappaB signaling
OT  - NLRC5
OT  - chondrocytes
OT  - inflammation
OT  - osteoarthritis
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2021/08/27 06:00
MHDA- 2022/02/02 06:00
PMCR- 2021/08/31
CRDT- 2021/08/26 20:30
PHST- 2021/03/13 00:00 [received]
PHST- 2021/08/14 00:00 [accepted]
PHST- 2021/08/27 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/08/26 20:30 [entrez]
PHST- 2021/08/31 00:00 [pmc-release]
AID - 203453 [pii]
AID - 10.18632/aging.203453 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 Aug 26;13(16):20651-20660. doi: 10.18632/aging.203453. 
      Epub 2021 Aug 26.