Swelling-activated ClC-3 activity regulates prostaglandin E <subscript>2</subscript> release in human OUMS-27 chondrocytes.
In: Biochemical and biophysical research communications, Jg. 537 (2021-01-22), S. 29
Online
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Zugriff:
Articular chondrocytes are exposed to dynamic osmotic environments during normal joint loading, and thus, require effective volume regulatory mechanisms. A regulatory volume decrease (RVD) is one of the mechanisms for protecting chondrocytes from swelling and damage. Swelling-activated Cl - currents (I Cl,swell ) are responsible for the RVD, but the molecular identity in chondrocytes is largely unknown. In this study, we reveal that in human OUMS-27 chondrocytes, I Cl,swell can be elicited by hypoosmotic stimulation (180 mOsm) and be inhibited by classical Cl - channel blockers, 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and niflumic acid, and be attenuated by siRNA knockdown of ClC-3. Our molecular analyses revealed that ClC-3A is expressed as a major splice variant in both human articular chondrocytes and OUMS-27 cells. The onset and early phase of RVD following hypoosmotic stress in OUMS-27 cells were affected by DIDS and ClC-3 knockdown. Hypoosmotic stimulation caused Ca 2+ influx and subsequent release of prostaglandin E 2 (PGE 2 ) in OUMS-27 cells, and both of these responses were reduced by DIDS and ClC-3 knockdown. These results strongly suggest that ClC-3 is responsible for I Cl,swell and RVD under the hypoosmotic environments. It is likely that ClC-3 is associated with the pathogenesis of cartilage degenerative diseases including osteoarthritis via PGE 2 release.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Titel: |
Swelling-activated ClC-3 activity regulates prostaglandin E <subscript>2</subscript> release in human OUMS-27 chondrocytes.
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Autor/in / Beteiligte Person: | Yamada, S ; Suzuki, Y ; Bernotiene, E ; Giles, WR ; Imaizumi, Y ; Yamamura, H |
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Zeitschrift: | Biochemical and biophysical research communications, Jg. 537 (2021-01-22), S. 29 |
Veröffentlichung: | <2002- >: San Diego, CA : Elsevier ; <i>Original Publication</i>: New York, Academic Press., 2021 |
Medientyp: | academicJournal |
ISSN: | 1090-2104 (electronic) |
DOI: | 10.1016/j.bbrc.2020.12.068 |
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