Fracture of the vertebral endplates, but not equienergetic impact load, promotes disc degeneration in vitro.
Vertebral endplate damage is associated with intervertebral disc (IVD) degeneration (DD) in vivo as confirmed by in-vitro investigations. Our aims were to further characterize the process of DD using an in vitro full-organ culture model and to elucidate whether significant endplate damage or impact loading alone is pivotal for the initiation of DD. Rabbit spinal segments (n = 80) were harvested, subjected to pure axial impact loading (n = 40) using a custom-made device, and cultured for 28 days. The applied threshold energy (0.76 J) induced endplate fractures in 21 specimens (group A); 19 remained intact (group B). Markers for DD (cell viability, apoptosis, necrosis, matrix remodeling, and inflammation) were monitored for 28 days post-trauma in the annulus fibrosus (AF) and nucleus pulposus and compared to non-impacted control discs. Cell viability in both groups stayed at a control level. Group A compared to group B showed enhanced lactate dehydrogenase (LDH) and caspase-3/7 activity, reduced glycosaminoglycan content, reduced aggrecan mRNA, but elevated mRNA for collagen-2, catabolic enzymes (MMP-1/-3/-13), and pro-inflammatory (TNFα, IL-6, IL-8, MCP-1) and pro-apoptotic (fas ligand, caspase-3) proteins. Group B compared to control only showed small changes in mRNA levels. Our findings demonstrate that burst endplates, but not equienergetic loading, promotes DD.
Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, CH-3014 Bern, Switzerland.
Stefan
S
Dudli
Daniel
D
Haschtmann
Stephen J
SJ
Ferguson
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000209:etiology* / Q000378:metabolism; D009336:Necrosis; D011817:Rabbits; D013124:Spinal Injuries / Q000150:complications*; D014158:Transcription, Genetic