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PLCγ1 deficiency in chondrocytes accelerates the age‐related changes in articular cartilage and subchondral bone.
- Source :
- Journal of Cellular & Molecular Medicine; Aug2024, Vol. 28 Issue 16, p1-14, 14p
- Publication Year :
- 2024
-
Abstract
- Ageing is the most prominent risk for osteoarthritis (OA) development. This study aimed to investigate the role of phosphoinositide‐specific phospholipase Cγ (PLCγ) 1, previously linked to OA progression, in regulating age‐related changes in articular cartilage and subchondral bone. d‐galactose (d‐Gal) was employed to treat chondrocytes from rats and mice or injected intraperitoneally into C57BL/6 mice. RTCA, qPCR, Western blot and immunohistochemistry assays were used to evaluate cell proliferation, matrix synthesis, senescence genes and senescence‐associated secretory phenotype, along with PLCγ1 expression. Subchondral bone morphology was assessed through micro‐CT. In mice with chondrocyte‐specific Plcg1 deficiency (Plcg1flox/flox; Col2a1‐CreERT), articular cartilage and subchondral bone were examined over different survival periods. Our results showed that d‐Gal induced chondrocyte senescence, expedited articular cartilage ageing and caused subchondral bone abnormalities. In d‐Gal‐induced chondrocytes, diminished PLCγ1 expression was observed, and its further inhibition by U73122 exacerbated chondrocyte senescence. Plcg1flox/flox; Col2a1‐CreERT mice exhibited more pronounced age‐related changes in articular cartilage and subchondral bone compared to Plcg1flox/flox mice. Therefore, not only does d‐Gal induce senescence in chondrocytes and age‐related changes in articular cartilage and subchondral bone, as well as diminished PLCγ1 expression, but PLCγ1 deficiency in chondrocytes may also accelerate age‐related changes in articular cartilage and subchondral bone. PLCγ1 may be a promising therapeutic target for mitigating age‐related changes in joint tissue. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15821838
- Volume :
- 28
- Issue :
- 16
- Database :
- Complementary Index
- Journal :
- Journal of Cellular & Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 179374675
- Full Text :
- https://doi.org/10.1111/jcmm.70027