Asporin regulated by miR-26b-5p mediates chondrocyte senescence and exacerbates osteoarthritis progression via TGF-ß1/Smad2 pathway.
Rheumatology (Oxford)
; 61(6): 2631-2643, 2022 05 30.
Article
in En
| MEDLINE
| ID: mdl-34559207
ABSTRACT
OBJECTIVES:
This study aimed to investigate the role and mechanism of asporin in modulating chondrocyte senescence in OA pathology.METHODS:
Asporin and senescence-related hallmark expression were examined in human and experimental OA mouse cartilage samples. Twelve-week-old male C57 mice were administered with recombinant protein (rm-asporin)- or asporin-siRNA-expressing lentiviruses via intra-articular injection once a week after destabilization of the medial meniscus (DMM) surgery to induce OA. Cartilage damage was measured using the Osteoarthritis Research Society International score. Senescence-associated ß-galactosidase (SA-ß-Gal) staining, γH2AX, p21 and p16INK4a were analysed by immunofluorescence staining and western blot to assess the specific role of asporin in chondrocyte senescence. The TGF-ß1-Smad2 signalling pathway and miR-26b-5p were further evaluated to explore the mechanism of asporin in OA.RESULTS:
Asporin was upregulated in articular chondrocytes of OA patients and DMM mice and accompanied by accumulation of senescent cells. Asporin overexpression exaggerated OA progression, whereas silencing asporin restored chondrocyte homeostasis and deferred chondrocyte senescence, leading to markedly attenuated DMM-induced OA. Cellular and molecular analyses showed that asporin can be inhibited by miR-26b-5p, which was significantly downregulated in OA cartilage, leading to exacerbation of experimental OA partially through inhibition of TGF-ß1-Smad2 signalling in chondrocytes.CONCLUSIONS:
Our findings indicate that asporin plays an essential role in chondrocyte senescence and OA pathogenesis. Upregulated by miR-26b-5p, asporin inhibits the TGF-ß1-Smad2 pathway to accelerate chondrocyte senescence and exacerbate cartilage degeneration. Targeting the miR-26b-5p-asporin-Smad2 axis may serve as a practical therapeutic strategy to delay chondrocyte senescence and OA development.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoarthritis
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Cartilage, Articular
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MicroRNAs
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Rheumatology (Oxford)
Journal subject:
REUMATOLOGIA
Year:
2022
Document type:
Article