Intermittent Cyclic Mechanical Tension Promotes Degeneration Of Endplate Cartilage Via The Nuclear Factor-?B Signaling Pathway:An In Vivo Study

Objective: To establish a rabbit model for investigating the potential effects of intermittent cyclic mechanical tension(ICMT)and NF-?B signaling pathway on promoting degeneration of endplate cartilage.Methods: Forty New Zealand white rabbits were subjected to surgery and randomly divided into three equal groups as follows: control group(no treatment,n = 10),sham group(animals underwent a sham operation but were not sub jected to mechanical tensile strain,n = 15)and loaded group(discs were subjected to 1.5 MPa external tensile loading by using an external loading device during the animals' daily activity,n = 15).Mechanical tensile strain was applied for 8 h/d.The animals were examined radiologically after 8 weeks treatment and then killed for removal of endplate cartilage tissue samples from their spines.Histological staining was performed to examine the morphology of endplate cartilage tissue.Multiple strategies were employed to examine degeneration of endplate cartilage and nuclear factor(NF)-?B signaling pathway activation.Results: After ICMT loading for 56 days,radiology revealed ossification,hyperosteogeny and stenosis in the intervertebral spaces.Examination of hematoxylin and eosin staining of sections of endplate cartilage showed significant damage as the load duration increased in the ICMT loading group.Expression of aggrecan(ACAN),type II collagen(COL-2A),SRY-related high mobility group-box gene 9(SOX9)was down-regulated,whereas that of matrix metallopeptidase 13(MMP13)and runt-related transcription factor 2(RUNX2)was up-regulated after ICMT.Western blot and immunofluorescence revealed that expression of protein was consistent with gene expression results.Additionally,ICMT can result in NF-?B signaling pathway activation along with endplate cartilage degeneration.Conclusions: These experiments indicate that ICMT contributes to the activation of NF-?B signaling pathway in vivo and that the NF-?B signaling pathway further up-regulates MMP13 and RUNX2,leading to degeneration of endplate cartilage.