Krüppel-like factor-4 and Krüppel-like factor-2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis.
Chondrocytes
Inflammation
Osteoarthritis
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
09 May 2022
09 May 2022
Historique:
received:
16
11
2021
accepted:
24
04
2022
entrez:
9
5
2022
pubmed:
10
5
2022
medline:
10
5
2022
Statut:
aheadofprint
Résumé
Analysing expression patterns of Krüppel-like factor (KLF) transcription factors in normal and osteoarthritis (OA) human cartilage, and determining functions and mechanisms of KLF4 and KLF2 in joint homoeostasis and OA pathogenesis. Experimental approaches included human joint tissues cells, transgenic mice and mouse OA model with viral KLF4 gene delivery to demonstrate therapeutic benefit in structure and pain improvement. Mechanistic studies applied global gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq). Several KLF genes were significantly decreased in OA cartilage. Among them, KLF4 and KLF2 were strong inducers of cartilage collagen genes and Proteoglycan-4. Cartilage-specific deletion of KLF4 and KLF2 may be central transcription factors that increase protective and regenerative functions in joint tissue cells, suggesting that KLF gene transfer or molecules upregulating KLFs are therapeutic candidates for OA.
Identifiants
pubmed: 35534137
pii: annrheumdis-2021-221867
doi: 10.1136/annrheumdis-2021-221867
pmc: PMC9643672
mid: NIHMS1802905
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : R01 AG049617
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056144
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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