LncRNA HAGLR activates RUNX2 and inhibits NLRP3 inflammasome to promote tibial fracture healing
10.19405/j.cnki.issn1000-1492.2023.05.021
- Author:
Wen Wang
1
;
Xinyu Chen
1
;
Ziyi Huang
1
;
Yangliu Deng
1
;
Hongwang Cui
1
Author Information
1. Emergency and Trauma Surgery , The First Afiliated Hospital of Hainan Medical College , Haikou 570100
- Publication Type:Journal Article
- Keywords:
tibial fracture;
homeobox D gene cluster antisense growth⁃related long non⁃coding RNA;
Runt⁃related ranscription factor 2;
NOD⁃like receptor pyrin domain⁃associated protein 3;
inflammasome
- From:
Acta Universitatis Medicinalis Anhui
2023;58(5):830-837
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of long non⁃coding RNA (LncRNA) HAGLR on the expression of NODlike receptor pyrin domain⁃associated protein 3 ( NLRP3 ) inflammasome and fracture healing in tibial fracture (TF) mice and to explore the mechanism .
Methods :First , HAGLR in osteoblast MC3T3 ⁃E1 was silenced by in vitro . Cell viability was detected by CCK⁃8 assay , cell apoptosis was detected by TUNEL assay , and the expressions of bone alkaline phosphatase (BALP) and osteocalcin were detected by qPCR . Western blot assay was used to detect the expressions of RUNX2 , phosphorylated RUNX2 ( p ⁃RUNX2 ) , NLRP3 , cysteine aspartic protease 1 (Caspase1) , apoptosis⁃associated spot⁃like protein ( ASC) and interleukin⁃1β . TF mouse models were established by tibial fracture operation in mice . HAGLR was overexpressed in the model mice , and RUNX2 was silenced or an inflammatory body inhibitor MCC950 was added on the basis of overexpression of HAGLR . The expressions of HAGLR and RUNX2 were detected by qPCR , and the expressions of insulin⁃like growth factor (IGF⁃1) were detected by Western blot . microCT was used to measure the volume of mouse callus (MBV) and the total tibial wet weight .
Results :The apoptosis rate of MC3T3 ⁃E1 cells increased and the expression levels of RUNX2 ,p⁃RUNX2 , BALP and osteocalcin decreased ( P < 0. 05 ) . The expressions of NLRP3 , Caspase1 , ASC and IL⁃1β increased ( P <0. 05) . Compared with healthy tissue , the expressions of HAGLR and RUNX2 in TF mice decreased . Overexpression of HAGLR promoted the expressions of HAGLR and RUNX2 in TF mice , and increased the expression of MBV and tibia wet weight and IGF⁃1 (P < 0. 05) . Silencing RUNX2 on the basis of overexpression of HAGLR resulted in decreased expression of MBV , tibial wet weight and IGF⁃1 in TF mice (P < 0. 05) . However , the addition of NLRP3 inflammasome inhibitor MCC950 on top of the overexpression of HAGLR resulted in increased expressions of MBV , full⁃length tibia wet weight and IGF⁃1 (P < 0. 05) .
Conclusion:LncRNA HAGLR promotes the healing of tibial fractures by activating RUNX2 and inhibiting NLRP3 inflammasome .
- Full text:2024081321192577743LncRNA_HAGLR激...症小体对胫骨骨折愈合的影响_王文.pdf
