Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells

Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCT-positive subpopulation and sho...

Full description

Saved in:
Bibliographic Details
Published inJournal of Veterinary Medical Science Vol. 85; no. 11; pp. 1237 - 1244
Main Authors ITOH, Harumichi, TANI, Kenji, SUNAHARA, Hiroshi, NEMOTO, Yuki, NAKAICHI, Munekazu, HORIKIRIZONO, Hiro, ITAMOTO, Kazuhito
Format Journal Article
LanguageEnglish
Published Tokyo JAPANESE SOCIETY OF VETERINARY SCIENCE 2023
Japan Science and Technology Agency
The Japanese Society of Veterinary Science
Subjects
adipose-derived stem cell
Cell differentiation
Cell proliferation
cystine-glutamate transporter
Gene expression
Glutamic acid transporter
Glutathione
Intracellular
osteogenic differentiation
Oxidative stress
Regenerative medicine
Rheumatoid arthritis
Stem cells
Sulfasalazine
Surgery
Online AccessGet full text

Cover

More Information
Summary:Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCT-positive subpopulation and show relatively low expression of osteogenic markers during in vitro osteogenic differentiation. Sulfasalazine (SSZ), a drug used to treat rheumatoid arthritis, suppresses xCT expression in cancer cells. In this study, we found that the SSZ treatment at 100 µM significantly suppressed xCT mRNA expression in CADSCs but did not significantly affect cell proliferation under the same conditions. Additionally, this treatment decreased the intracellular glutathione concentration. During in vitro osteogenic differentiation, the SSZ treatment at 50 µM and 100 µM significantly increased alizarin red staining and its quantification, as well as the concentration-dependent osteogenic differentiation markers (BMP1 and SPP) mRNA expression. Our results suggested that SSZ enhances the osteogenic differentiation potential of CADSCs and can potentially exhibit a superior therapeutic profile in canine bone regenerative medicine.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0916-7250
1347-7439
DOI:10.1292/jvms.22-0525