Catabolic mediators from TLR2-mediated proteoglycan aggrecan peptide-stimulated chondrocytes are reduced by Lactobacillus-conditioned media.
Chondrocytes
/ metabolism
Humans
Toll-Like Receptor 2
/ metabolism
Aggrecans
/ metabolism
Culture Media, Conditioned
/ pharmacology
Lactobacillus
/ metabolism
Signal Transduction
/ drug effects
Osteoarthritis
/ metabolism
Cells, Cultured
ADAMTS4 Protein
/ metabolism
STAT3 Transcription Factor
/ metabolism
Peptides
/ pharmacology
Proteoglycans
/ metabolism
Matrix Metalloproteinase 1
/ metabolism
NF-KappaB Inhibitor alpha
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 Aug 2024
05 Aug 2024
Historique:
received:
20
09
2023
accepted:
23
07
2024
medline:
6
8
2024
pubmed:
6
8
2024
entrez:
5
8
2024
Statut:
epublish
Résumé
In osteoarthritis (OA), extracellular matrix (ECM) digestion by cartilage-degrading enzymes drives cartilage destruction and generates ECM fragments, such as proteoglycan aggrecan (PG) peptides. PG peptides have been shown to induce immunological functions of chondrocytes. However, the role of PG peptides in stimulating catabolic mediators from chondrocytes has not been investigated. Therefore, we aim to determine the effects and its mechanism by which PG peptides induce chondrocytes to produce catabolic mediators in OA. Human chondrocytes were stimulated with IFNγ and various PG peptides either (i) with or (ii) without TLR2 blockade or (iii) with Lactobacillus species-conditioned medium (LCM), a genus of bacteria with anti-inflammatory properties. Transcriptomic analysis, cartilage-degrading enzyme production and TLR2-intracellular signaling activation were investigated. Chondrocytes treated with PG peptides p16-31 and p263-280 increased expression levels of genes associated with chondrocyte hypertrophy, cartilage degradation and proteolytic enzyme production. TLR2 downstream signaling proteins (STAT3, IkBα and MAPK9) were significantly phosphorylated in p263-280 peptide-stimulated chondrocytes. MMP-1 and ADAMTS-4 were significantly reduced in p263-280 peptides-treated condition with TLR2 blockade or LCM treatment. Phosphorylation levels of IkBa, ERK1/2 and MAPK9 were significantly decreased with TLR2 blockade, but only phosphorylation levels of MAPK9 was significantly decreased with LCM treatment. Our study showed that PG peptide stimulation via TLR2 induced cartilage-degrading enzyme production via activation of MAPK, NFκB and STAT3 pathways.
Identifiants
pubmed: 39103466
doi: 10.1038/s41598-024-68404-9
pii: 10.1038/s41598-024-68404-9
doi:
Substances chimiques
Toll-Like Receptor 2
0
Aggrecans
0
Culture Media, Conditioned
0
TLR2 protein, human
0
ADAMTS4 Protein
EC 3.4.24.82
STAT3 Transcription Factor
0
Peptides
0
Proteoglycans
0
Matrix Metalloproteinase 1
EC 3.4.24.7
ADAMTS4 protein, human
EC 3.4.24.82
NF-KappaB Inhibitor alpha
139874-52-5
NFKBIA protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18043Subventions
Organisme : Ratchadaphiseksompotch Fund, Faculty of Medicine, Chulalongkorn University
ID : RA62/112
Informations de copyright
© 2024. The Author(s).
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