PMID- 35474736
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 28
DP  - 2022 Jun 14
TI  - MicroRNA-378 contributes to osteoarthritis by regulating chondrocyte autophagy 
      and bone marrow mesenchymal stem cell chondrogenesis.
PG  - 328-341
LID - 10.1016/j.omtn.2022.03.016 [doi]
AB  - Osteoarthritis (OA) is the most common joint disease; thus, understanding the 
      pathological mechanisms of OA initiation and progression is critical for OA 
      treatment. MicroRNAs (miRNAs) have been shown to be involved in the progression 
      of osteoarthritis, one candidate is microRNA-378 (miR-378), which is highly 
      expressed in the synovium of OA patients during late-stage disease, but its 
      function and the underlying mechanisms of how it contributes to disease 
      progression remain poorly understood. In this study, miR-378 transgenic (TG) mice 
      were used to study the role of miR-378 in OA development. miR-378 TG mice 
      developed spontaneous OA and also exaggerated surgery-induced disease 
      progression. Upon in vitro OA induction, miR-378 expression was upregulated and 
      correlated with elevated inflammation and chondrocyte hypertrophy. Chondrocytes 
      isolated from articular cartilage from miR-378 TG mice showed impaired 
      chondrogenic differentiation. The bone marrow mesenchymal stem cells (BMSCs) 
      collected from miR-378 TG mice also showed repressed chondrogenesis compared with 
      the control group. The autophagy-related protein Atg2a, as well as chondrogenesis 
      regulator Sox6, were identified as downstream targets of miR-378. Ectopic 
      expression of Atg2a and Sox6 rescued miR-378-repressed chondrocyte autophagy and 
      BMSC chondrogenesis, respectively. Anti-miR-378 lentivirus intra-articular 
      injection in an established OA mouse model was shown to ameliorate OA 
      progression, promote articular regeneration, and repress hypertrophy. Atg2a and 
      Sox6 were again confirmed to be the target of miR-378 in vivo. In conclusion, 
      miR-378 amplified OA development via repressing chondrocyte autophagy and by 
      inhibiting BMSCs chondrogenesis, thus indicating miR-378 may be a potential 
      therapeutic target for OA treatments.
CI  - (c) 2022 The Authors.
FAU - Feng, Lu
AU  - Feng L
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Yang, Zhengmeng
AU  - Yang Z
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Li, Yucong
AU  - Li Y
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Pan, Qi
AU  - Pan Q
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
AD  - Department of Pediatric Orthopaedics, South China Hospital, Health Science 
      Center, Shenzhen University, Shenzhen 518116, PR China.
FAU - Zhang, Xiaoting
AU  - Zhang X
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Wu, Xiaomin
AU  - Wu X
AD  - Department of Orthopaedics and Traumatology, People's Hospital of Baoan District, 
      The Second Affiliated Hospital of Shenzhen University, Shenzhen, PR China.
FAU - Lo, Jessica Hiu Tung
AU  - Lo JHT
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Wang, Haixing
AU  - Wang H
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Bai, Shanshan
AU  - Bai S
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Lu, Xuan
AU  - Lu X
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Wang, Ming
AU  - Wang M
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Lin, Sien
AU  - Lin S
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
FAU - Pan, Xiaohua
AU  - Pan X
AD  - Department of Orthopaedics and Traumatology, People's Hospital of Baoan District, 
      The Second Affiliated Hospital of Shenzhen University, Shenzhen, PR China.
FAU - Li, Gang
AU  - Li G
AD  - Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine 
      Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of 
      Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
LA  - eng
PT  - Journal Article
DEP - 20220323
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC9010521
OTO - NOTNLM
OT  - autophagy
OT  - chondrocytes
OT  - chondrogenesis
OT  - mesenchymal stem cells
OT  - miR-378
OT  - osteoarthritis
COIS- The authors declare no competing interests.
EDAT- 2022/04/28 06:00
MHDA- 2022/04/28 06:01
PMCR- 2022/03/23
CRDT- 2022/04/27 06:14
PHST- 2021/09/20 00:00 [received]
PHST- 2022/03/17 00:00 [accepted]
PHST- 2022/04/27 06:14 [entrez]
PHST- 2022/04/28 06:00 [pubmed]
PHST- 2022/04/28 06:01 [medline]
PHST- 2022/03/23 00:00 [pmc-release]
AID - S2162-2531(22)00065-8 [pii]
AID - 10.1016/j.omtn.2022.03.016 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2022 Mar 23;28:328-341. doi: 10.1016/j.omtn.2022.03.016. 
      eCollection 2022 Jun 14.