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ATF4 ‐modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy
Author(s) -
Wang Yan,
He ShiHao,
Liang Xu,
Zhang XinXin,
Li ShanShan,
Li TianFang
Publication year - 2021
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2414
Subject(s) - autophagy , atf4 , osteoarthritis , chondrocyte , medicine , cartilage , apoptosis , chemistry , pathology , unfolded protein response , anatomy , biochemistry , alternative medicine
Activating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene‐delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum‐derived exosomes from OA mice as the gene‐delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury‐induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham‐Exo and OA‐Exo, respectively. ATF4‐overexpressing OA‐Exo (ATF4‐OA‐Exo) was developed by introducing ATF4 mRNA into OA‐Exo via electroporation. Four weeks after surgery, OA mice received intra‐articular injections of sham‐Exo, OA‐Exo, and ATF4‐OA‐Exo, respectively. The results showed that intra‐articular injection of ATF4‐OA‐Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra‐articular injection of ATF4‐OA‐Exo. Further in vitro assays revealed that ATF4‐OA‐Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF‐α‐ or tunicamycin‐treated chondrocytes. Together, ATF4‐modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.