Bmi-1 Plays A Critical Role In Intervertebral Disc Degeneration Of Mice

Intervertebral disc degeneration is the major cause of lumar degenerative diseases and low back pain.To date,the traditional therapies of intervertebral disc degeneration are mainly to alleviate patient's clinical symptoms,there are not any treatment that can reverse degeneration or prevent it from getting worse.In recent years,numerous studies have demonstrated that genetic factors have great assocations with intervertebral disc degeneration.Previous studies have found that Bmi-1 deficiency decreases chondrocyte proliferation and increases chondrocyte apoptosis.We also found that Bmi-1-/-adult mice shows walking instability and spinal kyphosis.However,it is unknown whether Bmi-1 deficiency could lead to premature intervertebral disc degeneration in mice.To investigate the effects of Bmi-1 deficiency on intervertebral disc degeneration,we established Bmi-1 gene knockout mice model.We chose 8-week-old Bi-1-/-mice as experimental group and 8-week-old wild-type littermates as control group,and analyzed their disc phenotypes by X-ray,MRI and histochemical staining.Compared with wild-type littermates,Bmi-1-/-mice age 8 weeks exhibited typical disc degenerative phenotypes,including the increased physiological curvature of spine,the reduction of intervertebral disc signals in T2WI and the decline of height of intervertebral disc and endplate.We detected type X collagen and proteoglycan in intervertebral disc of 8-week-old Bmi-1-/-and wild-type mice.Results showed that type X collagen increased and proteoglycan declined significantly in Bmi-1-/-compared with wild-type littermates.To assess whether disc degeneration caused by Bmi-1 deficiency is dependent on cell apoptosis and oxidative stress,we analyzed apoptotic and oxidative stress related proteins in disc using immunohistochemistry and western blot.The findings showed that protein levels of Caspase-3,p53 were up-regulated apparently and protein levels of Bcl-2 were down-regulated in 8-week-old Bmi-1-/-mice,compared with 8-week-old wild-type littermates.In addition,Bmi-1-/-mice displayed the reduction of SOD-1 protein and the increase of TNF-a protein.These results demonstrated that Bmi-1 deficiency lead to premature intervertebral disc degeneration in mice,which might be due to the up-regulation of oxidative stress level and the increased disc cell apoptosis.This study merely expound the influence of Bmi-1 deficiency in intervertebral disc degeneration,provide a new target for gene therapy.The mechanism underlying the involvement of Bmi-1 deficiency in intervertebral disc degeneration need further investigation.