NOV/CCN3 induces cartilage protection by inhibiting PI3K/AKT/mTOR pathway.
Animals
Autophagy
/ physiology
Cartilage, Articular
/ metabolism
Cell Line, Tumor
Chondrocytes
/ metabolism
Humans
Inflammation
/ metabolism
Male
NF-kappa B
/ metabolism
Nephroblastoma Overexpressed Protein
/ metabolism
Osteoarthritis
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
/ physiology
TOR Serine-Threonine Kinases
/ metabolism
CCN3
HMGB1
IL-1β
MMPs
osteoarthritis
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
21
04
2019
revised:
26
07
2019
accepted:
07
08
2019
pubmed:
28
8
2019
medline:
12
9
2020
entrez:
28
8
2019
Statut:
ppublish
Résumé
Osteoarthritis (OA), an age-related degenerative joint disease, is pathologically characterized by articular cartilage degeneration and synovial inflammation. Nephroblastoma overexpressed (NOV or CCN3), a matricellular protein, is a primary member of the CCN family (Cyr61, Ctgf, NOV) of proteins and is involved in various inflammatory disorders. Previous studies reported that CCN3 might play a therapeutic role in OA. However, the underlying mechanism remains unclear. In this study, we confirmed the expression of CCN3 was decreased in human and rat OA articular cartilage. Recombinant CCN3 ameliorated the IL-1β-induced matrix catabolism, as demonstrated by MMP1, MMP3, MMP13, ADAMTS5 and iNOS expression, in vitro. In addition, the degradation of cartilage matrix such as collagen 2 and aggrecan could be reversed by CCN3. Furthermore, we found CCN3 promoted autophagy as Atg5, Beclin1 and LC3-II expression were increased. High-mobility group box 1 was negatively correlated with CCN3 in IL-1β-induced osteoarthritis responses, and HMGB1 is involved in the protective effect of CCN3 in OA. Moreover, CCN3 overexpression decreased the expression of HMGB1 and reversed the IL-1β induced MMPs production. Additionally, recombinant CCN3 or CCN3 overexpression attenuated the activation of PI3K/AKT/mTOR pathway induced by IL-1β. Our study presents new mechanisms of CCN3 in osteoarthritis and indicates that CCN3 can serve as a novel potential therapeutic target for osteoarthritis.
Identifiants
pubmed: 31454155
doi: 10.1111/jcmm.14621
pmc: PMC6815824
doi:
Substances chimiques
CCN3 protein, human
0
NF-kappa B
0
Nephroblastoma Overexpressed Protein
0
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7525-7534Informations de copyright
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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