Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

MiR-27b-3p Targeting BDNF Inhibits TrkB / CREB Signaling Pathway and Improves IL-1 β Induced Chondrocytic Inflammation

Version 1 : Received: 25 February 2021 / Approved: 26 February 2021 / Online: 26 February 2021 (09:38:28 CET)

How to cite: Ruan, C.; Cong, R.J.; Wang, M.; Wang, L.; Yu, Y.; Li, X.; Lv, H. MiR-27b-3p Targeting BDNF Inhibits TrkB / CREB Signaling Pathway and Improves IL-1 β Induced Chondrocytic Inflammation. Preprints 2021, 2021020602 (doi: 10.20944/preprints202102.0602.v1). Ruan, C.; Cong, R.J.; Wang, M.; Wang, L.; Yu, Y.; Li, X.; Lv, H. MiR-27b-3p Targeting BDNF Inhibits TrkB / CREB Signaling Pathway and Improves IL-1 β Induced Chondrocytic Inflammation. Preprints 2021, 2021020602 (doi: 10.20944/preprints202102.0602.v1).

Abstract

Knee Osteoarthritis (KOA) is a chronic disease characterized by progressive disability and joint pain. Meniscus chondrocytes apoptosis is the main cause of reduced chondrocyte number and self-repair function. The purpose of this study was to investigate the role of miR-27b-3p in KOA.In this study, we found that the expression of miR-27b-3p was downregulated in cultured IL-1β treated chondrocyte and cartilage tissues in KOA. KOA overexpression evidently reduced IL-1β induced chondrocyte apoptosis and caspase-3 and caspase-9 expression.The upregulated iNOS and COX-2 mRNA and proteins expression was also inhibited by miR-27b-3p mimics. The expression of nitric oxide, PGE2, TNF-α and IL-6 was also inhibited by miR-27b-3p mimics. The target gene of miR-27b-3p was confirmed to be BDNF. TrkB/CREB pathway was proved to be the downstream pathway of miR-27b-3p/BDNF axis.The apoptotic cell percentage and nitric oxide, PGE2, TNF-α and IL-6 expression was induced by BDNF+IL-1β. This induction was inhibited by miR-27b-3p mimics. The cartilage tissues stained with safranin O results showed miR-27b-3p greatly decreased KOA induced cartilage degradation. The expression of BDNF、TrkB and p-CREB was inhibited by len-miR-27b-3p. MiR-27b-3p also reduced the expression of TNF-α、IL-6 and Bax, and increased Bcl-2 expression. These results indicated miR-27b-3p could applied to inhibit the development of KOA and miR-27b-3p/BDNF/TrkB/CREB pathway could serve as novel treatment target to handle KOA.

Subject Areas

Knee Osteoarthrit; miR-27b-3p; TrkB/CREB; pathway; BDNF

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