MicroRNA-23a-3p promotes the development of osteoarthritis by directly targeting SMAD3 in chondrocytes.
Osteoarthritis (OA) is a common chronic degenerative joint disease. Progressive destruction of the integrity of articular cartilage is an important pathological feature, but treatment options that reverse this damage have not been developed. According to recent studies, microRNAs have important regulatory roles in the initiation and progression of OA. In the current study, the biological effects of miR-23a-3p and its expression in OA tissues were examined. We found that miR-23a-3p expression was obviously higher and SMAD3 expression was significantly lower in OA cartilage than in normal tissues. The hypomethylation status of CpG islands in the promoter region of miR-23a-3p was confirmed by methylation-specific polymerase chain reaction in OA cartilage tissues. Furthermore, a bioinformatics analysis and luciferase reporter assay identified SMAD3 as a target gene of miR-23a-3p and SMAD3 expression at both the protein and mRNA levels was inhibited by miR-23a-3p. A functional analysis demonstrated that miR-23a-3p overexpression suppresses type II collagen and aggrecan expression, while miR-23a-3p inhibition had the opposite effects. Small interfering RNA-mediated knockdown of SMAD3 reversed the effects of the miR-23a-3p inhibitor on the expression of type II collagen and aggrecan. Our results suggested that miR-23a-3p contributes to OA progression by directly targeting SMAD3, providing a potential therapeutic target for OA treatment.
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Liang
L
Kang
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cao
C
Yang
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yu
Y
Song
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Wei
W
Liu
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Kun
K
Wang
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Shuai
S
Li
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: zhangyukuncom@126.com.
Yukun
Y
Zhang
D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism*
C552430:MIRN23a microRNA, human; D035683:MicroRNAs; C497790:SMAD3 protein, human; D051900:Smad3 Protein
Extracellular matrix; Hypomethylation; Osteoarthritis; SMAD3; miR-23a-3p