TY - JOUR
T1 - LncRNA MM2P-induced, exosome-mediated transfer of Sox9 from monocyte-derived cells modulates primary chondrocytes
AU - Bai, Jinyu
AU - Zhang, Yingzi
AU - Zheng, Xin
AU - Huang, Man
AU - Cheng, Weinan
AU - Shan, Huajian
AU - Gao, Xiang
AU - Zhang, Mingchao
AU - Sheng, Lei
AU - Dai, Jun
AU - Deng, Yekun
AU - Zhang, Hong
AU - Zhou, Xiaozhong
N1 - Funding Information:
This study was also supported by the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_2532).
Funding Information:
We thank all the members involved in this study. This work was supported by the grants from the National Natural Science Foundation of China (81873995 and 81171712), Clinical Key Diseases Diagnosis and Therapy Special Foundation of Suzhou City (LCZX201904), A-type superior discipline Orthopedics of discipline construction supporting project in the Second Affiliated Hospital of Soochow University (XKTJ-XK202003), the Key Laboratory of Spinal Cord Injury Repair of Suzhou (SZS201807), the National Natural Science Youth Foundation of China (81902207), the Suzhou Young Science and Technology Project (KJXW2018012), Social Development Program of Jiangsu province (BE2019662), Gusu Medical Talents Program of Suzhou (20015), Health Commission of Jiangsu province (H2017066), the Natural Science Foundation of Jiangsu Province (Grant nos. BK20151213 and SBK2019040088), and Jiangsu Province Six Talent Peaks Project (No. SWYY-110).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Monocyte-derived cells were shown to promote cartilage repair in osteoarthritis. The role of the long non-coding RNA (lncRNA) MM2P in this function of monocyte-derived cells remained unexplored. Treatment of RAW264.7 murine macrophages and mouse bone marrow-derived macrophages with IL-4 or IL-13 upregulated MM2P expression, upstream of STAT3 and STAT6 phosphorylation. Specifically, MM2P blocked SHP2-mediated dephosphorylation of STAT3 at Try705 and interacted with the RNA-binding protein FUS. In turn, p-STAT3 increased the Sox9 gene expression. These cells released Sox9 mRNA and protein-containing exosomes, as demonstrated by a transmission electron microscope, nanoparticle tracking analysis, and detection of typical surface markers. Their culture supernatant promoted the differentiation of mouse primary chondrocytes, i.e., upregulated the expression of Col1a2 and Acan genes and promoted the secretion of extracellular matrix components proteoglycan and type II collagen. These effects were mediated by Sox9 mRNA and protein delivered to chondrocytes by exosomes. Together, ex vivo treatment of monocyte-derived cells with IL-4 or IL-13 promoted chondrocyte differentiation and functions through exosome-mediated delivery of Sox9 mRNA and protein.
AB - Monocyte-derived cells were shown to promote cartilage repair in osteoarthritis. The role of the long non-coding RNA (lncRNA) MM2P in this function of monocyte-derived cells remained unexplored. Treatment of RAW264.7 murine macrophages and mouse bone marrow-derived macrophages with IL-4 or IL-13 upregulated MM2P expression, upstream of STAT3 and STAT6 phosphorylation. Specifically, MM2P blocked SHP2-mediated dephosphorylation of STAT3 at Try705 and interacted with the RNA-binding protein FUS. In turn, p-STAT3 increased the Sox9 gene expression. These cells released Sox9 mRNA and protein-containing exosomes, as demonstrated by a transmission electron microscope, nanoparticle tracking analysis, and detection of typical surface markers. Their culture supernatant promoted the differentiation of mouse primary chondrocytes, i.e., upregulated the expression of Col1a2 and Acan genes and promoted the secretion of extracellular matrix components proteoglycan and type II collagen. These effects were mediated by Sox9 mRNA and protein delivered to chondrocytes by exosomes. Together, ex vivo treatment of monocyte-derived cells with IL-4 or IL-13 promoted chondrocyte differentiation and functions through exosome-mediated delivery of Sox9 mRNA and protein.
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U2 - 10.1038/s41419-020-02945-5
DO - 10.1038/s41419-020-02945-5
M3 - Article
C2 - 32938906
AN - SCOPUS:85091127885
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 9
M1 - 763
ER -