Influence Of Regulation Gene Expression Of Integrin β1 And Increase Height Of Fusion Cage On The Treatment Of Spinal Degenerative Diseases

Background: Mechanical factor plays an improtant role in the occurring,developing and treatment of spinal degenerative diseases.Integrin is a mechanical sensory receptor located on the cytomembrane,whose expression is down-regulated under stimulation of pathological mechanical stress.At the same time,it will improve adaptive capacity of intervertebral disc cell to pathological mechanical stress when the expression of integrin was artifically up-regulated.Local mechanical environment is improtant to the success of spinal fusion surgery.It is needed that sufficient segmental stability and appropriate load stimulate to the success of spinal fusion surgery.Objective: To study the feasibility of regulated integrin β1 gene,a mechanical sensory receptor,expression for suppression of nucleus pulposus cell apoptosis and intervertebral disc degeneration,and to determine the effect of the fusion cage height on both the stability and load sharing of the unilateral and bilateral instrumented transforaminal lumbar interbody fusion(TLIF)constructs.Methods: Rat nucleus pulposus(NP)cells were cultured,and were treated with levofoxacin to induce apoptosis.Integrin β1 over-expressing lentivirus vector(LV-ITG β1)was constructed and transduced to NP cells,and its effect on cell apoptosis were studied in vitro.Rat IVD degeneration model was developed,intradiscal injection of lentivirus vector was performed.The effect of integrin β1overexpression on the degree of disc degeneration was studied.Two sets of modular cages were designed for the flexibility and load sharing tests seperately to simulate the long and short cages.The effect of cage heigh variance on the flexibility and load sharing of the unilateral and bilateral fixation construts was studied.Results: LV-ITG β1 transfection signifcantly alleviated morphological changes of apoptosis,decreased apoptosis rate,and suppressed caspase-3 activity in vitro.LV-ITG β1 transfection in vivo alleviated the MRI score and histological grading scale of IVD degeneration,mitigated matrix proteoglycan degradation and decreased IVD cell apoptosis.When the fusion cage height decreased 2 mm,the segment flexibility with unilateral fixation showed a significant increase in the ROM for flexion–extension,lateral bending,and axial rotation of 74.9%,83.8%,and 175.2%(P< 0.01)respectively.In contrast,for bilateral fixation,the height decrease resulted in no significant change in ROM.Using a short fusion cage,the load bearing decreased in 17.1%,21.5%,and 54.1%(P < 0.05)for the cage alone,unilateral,and bilateral fixation respectively.Conclusion: Over-expression of the mechanical sensory receptor integrin β1 could effectively prevent NP cell apoptosis and pathological mechanical stress induced IVD degeneration.Incresement of the length of the fusion cage results in favourable mechanical enviroment facilated success fusion when performing TLIF with unilateral instrumentation.