Skp2/p27 axis regulates chondrocyte proliferation under high glucose induced endoplasmic reticulum stress.
Eur Rev Med Pharmacol Sci
; 24(17): 9129-9138, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32965004
ABSTRACT
OBJECTIVE:
Diabetes mellitus is closely related to osteoarthritis (OA) and may be an independent risk factor for the development of OA. As one of the main characteristics of diabetes, endoplasmic reticulum (ER) stress resulting from glucose metabolism disorder is one of the main causes of cartilage degeneration. The aim of our study is to illuminate the effect of high glucose to chondrocytes (CHs) and the role of Skp2 in high-glucose induced ER stress in CHs. PATIENTS ANDMETHODS:
We compared the ER stress status between healthy and diabetic OA cartilage using Western blot and quantitative reverse-transcription polymerase chain reaction (RT-PCR) methods. Different concentration of glucose was used to culture CHs for both 24 h and 72 h. Furthermore, Tunicamycin (TM) and 4-Phenylbutyric acid (4-PBA) were used to mediate ER stress of CHs, and human recombinant Skp2 protein was used to promote Skp2 expression. CH viability was determined by CCK8 assay, and cell proliferation was determined by flow cytometry. Western and RT-PCR were performed to measure related gene expression.RESULTS:
ER stress makers GADD34, GRP78, and MANF were upregulated in diabetic OA cartilage. The long-term high glucose increased GADD34, GRP78, and MANF expression, but decreased collagen II and proliferation of CHs, and Skp2 expression was negative related to the ER stress level. Additionally, Skp2 overexpression partly reversed ER stress-induced collagen II and proliferation suppression by the suppression of p27 expression.CONCLUSIONS:
High glucose raises the ER stress in CHs and overexpression of Skp2 promotes CH proliferation under high glucose treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Condrocitos
/
Proteínas Quinasas Asociadas a Fase-S
/
Inhibidor p27 de las Quinasas Dependientes de la Ciclina
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Eur Rev Med Pharmacol Sci
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China