miR-92a-3p-inspired shRNA exhibits pro-chondrogenic and chondrocyte protective effects in osteoarthritis treatment through targeting SMAD6/7.
J Bone Miner Metab
; 42(1): 1-16, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38055109
ABSTRACT
INTRODUCTION:
Osteoarthritis (OA) compromises patients' quality of life and requires further study. Although miR-92a-3p was reported to possess chondroprotective effects, the underlying mechanism requires further clarification. The objectives of this study were to elucidate the mechanism by which miR-92a-3p alleviates OA and to examine the efficacy of shRNA-92a-3p, which was designed based on mature miR-92a-3p. MATERIALS ANDMETHODS:
TargetScan and luciferase reporter assay were used to predict the target of miR-92a-3p. Adipose-derived stem cells (ADSCs) were transfected with miR-92a-3p/miR-NC mimic for the analysis of chondrogenic biomarkers and SMAD proteins. ADSCs and osteoarthritic chondrocytes were transduced with shRNA-92a-3p for the analysis of chondrogenic biomarkers and SMAD proteins. OA was surgically induced in C57BL/6JJcl mice, and ADSCs with/without shRNA-92a-3p transduction were intra-articularly injected for the assessment of cartilage damage.RESULTS:
SMAD6 and SMAD7 were predicted as direct targets of miR-92a-3p by TargetScan and luciferase reporter assay. Transfection of the miR-92a-3p mimic resulted in a decrease in SMAD6 and SMAD7 levels and an increase in phospho-SMAD2/3, phospho-SMAD1/5/9, SOX9, collagen type II, and aggrecan levels in ADSCs. Furthermore, shRNA-92a-3p decreased SMAD6 and SMAD7 levels, and increased phospho-SMAD2/3, phospho-SMAD1/5/9, SOX9, collagen type II, and aggrecan levels in ADSCs and osteoarthritic chondrocytes. Additionally, ADSC-shRNA-92a-3p-EVs reduced the rate of decrease of SOX9, collagen type II, and aggrecan in osteoarthritic chondrocytes. In mice with surgically induced OA, shRNA-92a-3p-treated ADSCs alleviated cartilage damage more effectively than nontreated ADSCs.CONCLUSIONS:
miR-92a-3p and shRNA-92a-3p exhibit therapeutic effects in treating OA by targeting SMAD6 and SMAD7, thereby enhancing TGF-ß signaling.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
MicroRNAs
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Bone Miner Metab
Assunto da revista:
METABOLISMO
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão