INTRODUCTION: NP cell apoptosis has been suggested to play an important role in disc degeneration. It has been proved Intervertebral disc cell apoptosis occurs through either death receptor, mitochondrial pathway or endoplasmic reticulum (ER) pathway. However, the relationship between the three apoptosis pathways and the grade of disc degeneration is unknown. The purpose of the current study is to evaluate the role of different apoptosis pathways in different stage of IVDD.
METHODS: 73 samples were collected from patients with intervertebral disc degeneration or trauma patients as control. IVDD was graded by MRI using the Pfirrmann Grading System. The histology of IVD was detected by H&E staining, NP cell apoptosis by TUNEL staining. Gene expression of the three apoptosis pathways was determined by RT‐PCR for FasL/Fas, P53, Bcl‐2, Bax and GRP78. IHC was used to detect the expression site of Cyt‐C.
RESULTS: Cell density of NP cells decreased with the promoting of degeneration process. More apoptotic cells with the promotion of degeneration. Fas expression was high in normal disc and higher in degenerative intervertebral disc, but little difference with the levels of degeneration. Almost no expression of FasL, Bax and p53mRNA in normal disc, whereas Higher grades of IVDD were accompanied by higher expression of FasL, Bax and p53. Almost no expression of GRP78 in normal disc, whereas GRP78 expression was detectable in IVDD but showed no significant change during the degeneration progressed. Bcl‐2 was detected with high expression in normal disc, but downregulated with the degeneration progressed.
CONCLUSION: Our preliminary results imply that IVDD may be promoted by the intrinsic mitochondria/ER and extrinsic Death receptor apoptosis signaling pathways. Death receptor pathway plays an important role in each stage of IVDD, ER pathway is involved in both stages especially early stage, mitochondria pathway plays an important role in the late stage.