MiR-1283 improves immune-inflammatory response and bone loss in rats with spinal cord injury secondary to osteoporosis by inhibiting the ATF4/CHOP signaling pathway
WANG Bufei
CHEN Cong
LI Jianhong
Abstract：Objective To investigate the effect and mechanism of microRNA(miR)-1283 on immune-inflammatory response and bone loss in rats with spinal cord injury secondary to osteoporosis(SCI-OP).Methods A total of 80 male adult Sprague-Dawley(SD)rats were randomly divided into the SCI-OP model group(n=70)and sham group(n=10).SCI-OP was established by total spinal cord transection at T10,and sham operation was performed with only skin incision and suture.At 10 days postoperatively,40 randomly selected SCI-OP rats were randomly divided into 4 groups,including SCI-OP+miR-1283-mimic group,SCI-OP+negative control(NC)-mimic group,SCI-OP+pcDNA3.1 empty vector(pcDNA-null)+miR-1283-mimic group,and SCI-OP+pcDNA3.1-ATF4 overexpression vector(pcDNA-ATF4)+miR-1283-mimic group,with 10 in each group.After 10 days of treatment,the bone volume fraction(BV/TV),trabecular bone number(Tb.N),trabecular bone spacing(Tb.Sp),and trabecular bone thickness(Tb.Th)were detected by microCT.Reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expressions of miR-1283,interleukin-1 beta(IL-1beta),IL-6,and tumor necrosis factor-alpha(TNF-alpha),and soluble interleukin 2 receptor(sIL-2R).Western blot was used to detect the protein expressions of transcription activator(ATF)4,phosphorylated activating transcription factor 4(p-ATF4),CCAT-enhancer-binding protein homologous protein(CHOP),and phosphorylated CHOP(p-CHOP).The direct regulatory relationship between miR-1283 and ATF4 was detected by dual-luciferase reporter assay.Results Compared with the sham group,rats in the SCI-OP group had significantly lower miR-1283 level,BV/TV,Tb.N and Tb.Th,but higher Tb.Sp,and expression levels of TNF-α,IL-6,IL-1β,IFN-γ,sIL-2R,ATF4,p-ATF4,CHOP and p-CHOP(allP＜0.05).Compared with the SCI-OP+NC-mimic group,rats in the SCI-OP+miR-1283-mimic group had significantly higher miR-1283 level,BV/TV,Tb.N and Tb.Th,and those in the SCI-OP+miR-1283-mimic group had significantly lower Tb.Sp,and expression levels of TNF-α,IL-6,IL-1β,IFN-γ,sIL-2R,ATF4,p-ATF4,CHOP and p-CHOP(allP＜0.05).ATF4 was the target gene of miR-1283.Compared with the pcDNA-null+miR-1283-mimic group,rats in the SCI-OP+pcDNA-ATF4+miR-1283-mimic group had significantly lower BV/TV,Tb.N and Tb.Th,and those in the SCI-OP group had significantly higher Tb.Sp,and expression levels of TNF-α,IL-6,IL-1β,IFN-γ,sIL-2R,ATF4,p-ATF4,CHOP and p-CHOP(allP＜0.05).Conclusion Overexpression of miR-1283 alleviates bone loss and immune inflammatory response in SCI-OP rats by targeting ATF4 and mediating the ATF4/CHOP signaling pathway.
Keywords：microRNA-1283osteoporosis secondary to spinal cord injurybone lossimmune inflammationactivator of transcription(ATF)4CCAT/enhancer-binding protein homologous protein(CHOP)
Publication Date：2025-04-26
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 540-545 )