PMID- 33404840
OWN - NLM
STAT- MEDLINE
DCOM- 20211022
LR  - 20211022
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Linking)
VI  - 384
IP  - 1
DP  - 2021 Apr
TI  - TGF-beta1-modified MSC-derived exosomal miR-135b attenuates cartilage injury via 
      promoting M2 synovial macrophage polarization by targeting MAPK6.
PG  - 113-127
LID - 10.1007/s00441-020-03319-1 [doi]
AB  - Osteoarthritis (OA) is the most common joint disease with an unsatisfactory 
      therapy outcome and characterized by the degradation of articular cartilage and 
      synovial inflammation. Here, we isolated bone marrow mesenchymal stem cells 
      (BMSCs) from rat's bone marrow and BMSC-derived exosome (BMSCs-Exo) from BMSCs 
      successfully. MiR-135b was proved to be highly expressed in TGF-beta1-stimulated 
      BMSC-derived exosomes (BMSCs-Exo(TGF-beta1)). Then, our results demonstrated that 
      BMSCs-Exo(TGF-beta1) reduced OA-induced upregulation of pro-inflammatory factors in 
      rat's serum and damage in cartilage tissues, which was then reversed by miR-135b 
      decreasing. Subsequently, we found that the OA-resulted M1 polarization of 
      synovial macrophages (SMs) was repressed by BMSCs-Exo(TGF-beta1), this effect of 
      BMSCs-Exo(TGF-beta1) was limited by miR-135b decreasing. We also proved that M2 
      polarization of SMs can be induced by miR-135b mimics. Furthermore, we found that 
      the promotory effect of miR-135b and BMSCs-Exo(TGF-beta1) on M2 SMs polarization was 
      reversed by increasing of MAPK6. Overall, our data showed that BMSCs-Exo(TGF-beta1) 
      attenuated cartilage damage in OA rats through carrying highly expressed 
      miR-135b. Mechanistically, miR-135b promoted M2 polarization of SMs through 
      targeting MAPK6, thus improving cartilage damage. Our study provided a novel 
      regulatory mechanism of BMSCs-Exo in OA development and revealed a new potential 
      treatment target of OA.
FAU - Wang, Rui
AU  - Wang R
AD  - Department of Sports Trauma & Arthroscopy, The First Affiliated Hospital of Anhui 
      Medical University, No. 218 Jixi Road, Hefei, Anhui, 230022, People's Republic of 
      China.
FAU - Xu, Bin
AU  - Xu B
AUID- ORCID: 0000-0002-5483-3943
AD  - Department of Sports Trauma & Arthroscopy, The First Affiliated Hospital of Anhui 
      Medical University, No. 218 Jixi Road, Hefei, Anhui, 230022, People's Republic of 
      China. binxu0709@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210106
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (MIRN135 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 6)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - MicroRNAs/*metabolism
MH  - Mitogen-Activated Protein Kinase 6/*metabolism
MH  - Osteoarthritis/genetics/metabolism/pathology/*therapy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transfection
MH  - Transforming Growth Factor beta1/*metabolism
OTO - NOTNLM
OT  - Bone marrow mesenchymal stem cells
OT  - Cartilage injury
OT  - Exosome
OT  - MiR-135b
OT  - Osteoarthritis
EDAT- 2021/01/07 06:00
MHDA- 2023/02/25 06:00
CRDT- 2021/01/06 12:19
PHST- 2020/07/14 00:00 [received]
PHST- 2020/10/06 00:00 [accepted]
PHST- 2021/01/07 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/01/06 12:19 [entrez]
AID - 10.1007/s00441-020-03319-1 [pii]
AID - 10.1007/s00441-020-03319-1 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2021 Apr;384(1):113-127. doi: 10.1007/s00441-020-03319-1. Epub 
      2021 Jan 6.