Possible Repositioning of an Oral Anti-Osteoporotic Drug, Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase.
CEMIP
KIAA1199
collagen-induced arthritis
hyaluronan
hyaluronidase
inflammatory arthritis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
07 Apr 2022
07 Apr 2022
Historique:
received:
09
03
2022
revised:
02
04
2022
accepted:
05
04
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
KIAA1199 has a strong hyaluronidase activity in inflammatory arthritis. This study aimed to identify a drug that could reduce KIAA1199 activity and clarify its effects on inflammatory arthritis. Rat chondrosarcoma (RCS) cells were strongly stained with Alcian blue (AB). Its stainability was reduced in RCS cells, which were over-expressed with the KIAA1199 gene (RCS-KIAA). We screened the drugs that restore the AB stainability in RCS-KIAA. The effects of the drug were evaluated by particle exclusion assay, HA ELISA, RT-PCR, and Western blotting. We further evaluated the HA accumulation and the MMP1 and three expressions in fibroblast-like synoviocytes (FLS). In vivo, the effects of the drug on symptoms and serum concentration of HA in a collagen-induced arthritis mouse were evaluated. Ipriflavone was identified to restore AB stainability at 23%. Extracellular matrix formation was significantly increased in a dose-dependent manner (
Identifiants
pubmed: 35456905
pii: ijms23084089
doi: 10.3390/ijms23084089
pmc: PMC9030858
pii:
doi:
Substances chimiques
Isoflavones
0
ipriflavone
80BJ7WN25Z
Hyaluronic Acid
9004-61-9
Hyaluronoglucosaminidase
EC 3.2.1.35
Matrix Metalloproteinase 1
EC 3.4.24.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology of Japan
ID : 20K18060 for Young Scientists
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