Swelling-activated ClC-3 activity regulates prostaglandin E2 release in human OUMS-27 chondrocytes.
In: Biochemical & Biophysical Research Communications, Jg. 537 (2021-01-22), S. 29-35
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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 Ca2+ 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. • Articular chondrocytes are exposed to hypoosmotic environments in osteoarthritis. • ClC-3 is responsible for swelling-activated Cl− currents in OUMS-27 chondrocytes. • ClC-3 contributes to the onset and early phase of the regulatory volume decrease. • Hypoosmotic solution-induced ClC-3 activation facilitates prostaglandin E 2 release. • ClC-3 may be a novel therapeutic target for osteoarthritis. [ABSTRACT FROM AUTHOR]
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Swelling-activated ClC-3 activity regulates prostaglandin E2 release in human OUMS-27 chondrocytes.
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Autor/in / Beteiligte Person: | Yamada, Satoshi ; Suzuki, Yoshiaki ; Bernotiene, Eiva ; Giles, Wayne R. ; Imaizumi, Yuji ; Yamamura, Hisao |
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Zeitschrift: | Biochemical & Biophysical Research Communications, Jg. 537 (2021-01-22), S. 29-35 |
Veröffentlichung: | 2021 |
Medientyp: | academicJournal |
ISSN: | 0006-291X (print) |
DOI: | 10.1016/j.bbrc.2020.12.068 |
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