Clusterin secretion is attenuated by the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in models of cartilage degradation.
Animals
Cartilage, Articular
/ metabolism
Chondrocytes
/ metabolism
Clusterin
/ genetics
Glycosaminoglycans
/ metabolism
Horses
Interleukin-1beta
/ pharmacology
Matrix Metalloproteinase 13
/ physiology
Matrix Metalloproteinase 3
/ physiology
Osteoarthritis
/ metabolism
Protein Isoforms
Tumor Necrosis Factor-alpha
/ pharmacology
apolipoprotein J
articular cartilage
biomarker
chondrocyte
clusterin
osteoarthritis (OA)
proteomics
secretome
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
17
06
2020
received:
24
04
2020
accepted:
27
07
2020
pubmed:
30
7
2020
medline:
4
9
2021
entrez:
30
7
2020
Statut:
ppublish
Résumé
The protein clusterin has been implicated in the molecular alterations that occur in articular cartilage during osteoarthritis (OA). Clusterin exists in two isoforms with opposing functions, and their roles in cartilage have not been explored. The secreted form of clusterin (sCLU) is a cytoprotective extracellular chaperone that prevents protein aggregation, enhances cell proliferation and promotes viability, whereas nuclear clusterin acts as a pro-death signal. Therefore, these two clusterin isoforms may be putative molecular markers of repair and catabolic responses in cartilage and the ratio between them may be important. In this study, we focused on sCLU and used established, pathophysiologically relevant, in vitro models to understand its role in cytokine-stimulated cartilage degradation. The secretome of equine cartilage explants, osteochondral biopsies and isolated unpassaged chondrocytes was analyzed by western blotting for released sCLU, cartilage oligomeric protein (COMP) and matrix metalloproteinases (MMP) 3 and 13, following treatment with the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α. Release of sulfated glycosaminoglycans (sGAG) was determined using the dimethylmethylene blue assay. Clusterin messenger RNA (mRNA) expression was quantified by quantitative real-time polymerase chain reaction. MMP-3, MMP-13, COMP, and sGAG release from explants and osteochondral biopsies was elevated with cytokine treatment, confirming cartilage degradation in these models. sCLU release was attenuated with cytokine treatment in all models, potentially limiting its cytoprotective function. Clusterin mRNA expression was down-regulated 7-days post cytokine stimulation. These observations implicate sCLU in catabolic responses of chondrocytes, but further studies are required to evaluate its role in OA and its potential as an investigative biomarker.
Substances chimiques
Clusterin
0
Glycosaminoglycans
0
Interleukin-1beta
0
Protein Isoforms
0
Tumor Necrosis Factor-alpha
0
Matrix Metalloproteinase 13
EC 3.4.24.-
Matrix Metalloproteinase 3
EC 3.4.24.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1017-1029Subventions
Organisme : Arthritis Research UK
ID : 20194
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
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