PMID- 32705163
OWN - NLM
STAT- MEDLINE
DCOM- 20210601
LR  - 20210601
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 46
IP  - 3
DP  - 2020 Sep
TI  - Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of 
      nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with 
      intervertebral disc degeneration.
PG  - 1074-1084
LID - 10.3892/ijmm.2020.4668 [doi]
AB  - Intervertebral disc degeneration (IDD) is a condition involving disruption of the 
      bone tissue distribution. Nucleus pulposus mesenchymal stem cells (NPMSCs) and 
      Sirtuin 1 (SIRT1) play important roles in bone diseases, therefore the aim of the 
      present study was to evaluate the roles of SIRT1 and NPMSCs in IDD. First, NPMSCs 
      were harvested from patients with IDD. Then, the NPMSCs were treated with a SIRT 
      activator, and monocyte chemoattractant protein 1 (MCP1) and chemokine receptor 2 
      (CCR2) inhibitors. Indices related to NPMSC growth, proliferation, 
      differentiation and apoptosis were measured. Subsequently, IDD rat models were 
      established and were transfected with NPMSCs overexpressing SIRT1. NPMSC 
      apoptosis and cartilage differentiation were detected in the rat IDD model. SIRT1 
      expression was found to be decreased, and the expression of MCP1 and CCR2 
      increased in NPMSCs of patients with IDD. The upregulation of SIRT1 and the 
      downregulation of the MCP1/CCR2 axis promoted cartilage differentiation and 
      reduced the number of apoptotic NPMSCs. Furthermore, MCP1 reversed the 
      progression of the cartilage differentiation of NPMSCs and the inhibition of 
      NPMSC apoptosis induced by SIRT1 overexpression. Moreover, the transplantation of 
      rat NPMSCs overexpressing SIRT1 relieved IDD in rats. Therefore, SIRT1 
      overexpression improved cartilage differentiation and reduced the apoptosis of 
      NPMSCs by inactivating the MCP1/CCR2 axis, thus attenuating IDD in rats.
FAU - Ou, Xuancheng
AU  - Ou X
AD  - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 
      Guangdong 510515, P.R. China.
FAU - Ying, Jinwei
AU  - Ying J
AD  - Department of Orthopedic Surgery, The First Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou, Zhejiang 325000, P.R. China.
FAU - Bai, Xuedong
AU  - Bai X
AD  - Department of Orthopedic Surgery, The Sixth Medical Centre of PLA General 
      Hospital, Beijing 100048, P.R. China.
FAU - Wang, Chaofeng
AU  - Wang C
AD  - Department of Orthopedic Surgery, The Sixth Medical Centre of PLA General 
      Hospital, Beijing 100048, P.R. China.
FAU - Ruan, Dike
AU  - Ruan D
AD  - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 
      Guangdong 510515, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200703
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Apoptosis
MH  - Cartilage/metabolism/pathology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Chondrogenesis
MH  - Female
MH  - Humans
MH  - Intervertebral Disc Degeneration/genetics/*metabolism/pathology
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/metabolism/pathology
MH  - Middle Aged
MH  - Nucleus Pulposus/cytology/metabolism/pathology
MH  - Rats, Sprague-Dawley
MH  - Receptors, CCR2/*metabolism
MH  - *Signal Transduction
MH  - Sirtuin 1/genetics/*metabolism
MH  - Up-Regulation
PMC - PMC7387093
EDAT- 2020/07/25 06:00
MHDA- 2021/06/02 06:00
PMCR- 2020/07/03
CRDT- 2020/07/25 06:00
PHST- 2020/01/17 00:00 [received]
PHST- 2020/05/07 00:00 [accepted]
PHST- 2020/07/25 06:00 [entrez]
PHST- 2020/07/25 06:00 [pubmed]
PHST- 2021/06/02 06:00 [medline]
PHST- 2020/07/03 00:00 [pmc-release]
AID - ijmm-46-03-1074 [pii]
AID - 10.3892/ijmm.2020.4668 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Sep;46(3):1074-1084. doi: 10.3892/ijmm.2020.4668. Epub 2020 
      Jul 3.