Kartogenin mediates cartilage regeneration by stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells.
Anilides
/ pharmacology
Animals
Cartilage, Articular
/ cytology
Cell Proliferation
/ drug effects
Chondrocytes
/ cytology
Chondrogenesis
/ drug effects
Disease Models, Animal
Gene Expression
/ drug effects
In Vitro Techniques
Interleukin-6
/ genetics
Male
Osteoarthritis
/ drug therapy
Phthalic Acids
/ pharmacology
Rats
Regeneration
/ drug effects
STAT3 Transcription Factor
/ genetics
Signal Transduction
/ drug effects
Stem Cells
/ cytology
Cartilage regeneration
Cartilage stem/progenitor cells (CSPCs)
IL-6/Stat3 signalling
Kartogenin (KGN)
Proliferation
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
12 11 2020
12 11 2020
Historique:
received:
29
07
2020
accepted:
14
08
2020
pubmed:
6
9
2020
medline:
17
3
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
A decrease in the number of endogenous stem cells in cartilage is regarded as the cause of cartilage degeneration. Kartogenin (KGN) is known to induce chondrogenesis of cartilage stem/progenitor cells (CSPCs). Using CSPCs isolated from rat cartilage, we analysed changes in the transcriptome after treatment with KGN in vitro. An animal model of destabilization of the medial meniscus (DMM) was then used to identify the effect of intra-articular (IA) KGN injection on CSPC proliferation in vivo. Here, we demonstrated that KGN promoted the proliferation of CSPCs isolated from cartilage. The percentage of G2-M phase cells in the KGN-treated group reached over 10%, nearly twice that in the control group. Transcriptomic profiling of rat CSPCs revealed significant changes in KGN-treated samples compared to control samples. The gene expression levels of IL-6 and its coreceptor Gp130 were much higher in the KGN-treated group than in the control group. Phosphorylation of the IL-6 downstream molecule Stat3 was enhanced via KGN stimulation. The DMM animal model showed increased articular cartilage thickness after IA KGN injection. IHC staining also demonstrated upregulation of Stat3 phosphorylation and enhanced distribution of CD44
Identifiants
pubmed: 32888652
pii: S0006-291X(20)31646-6
doi: 10.1016/j.bbrc.2020.08.059
pii:
doi:
Substances chimiques
Anilides
0
Il6 protein, rat
0
Interleukin-6
0
Phthalic Acids
0
STAT3 Transcription Factor
0
Stat3 protein, rat
0
kartogenin
Q93BBN11CP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
385-392Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.