Table 2.

Summary of enzymatic and mechanical disc degeneration (= “catabolic shift”) experiments.

Stress factor	Organ Culture	Animal Model	Outcome	Reference
Enzymatic Degeneration Models
Injection of Catabolic Enzymes: Papain	BEP	Bovine coccygeal	↑ Injection of MSC, cell survival was improved in papain digested IVDs, MSC differentiated toward IVD phenotype	[77,78,91,108]
Injection of Catabolic Enzymes: Trypsin	BEP	Bovine coccygeal	↑ cell viability for osmotically loaded IVDs compared to isotonic IVDs	[33,80,108,109]
Injection of HTRA1, MMP3 and ADAMTS4	BEP	Bovine coccygeal	No major cavity formed, no major changes in disc matrix observed in histology	[110]
Injection of chodroitinase ABC	BEP	Coat, rabbit, rat coccygeal	Altered mechanical loading, secondary to biochemical changes in the NP	[106,107,131,132]
Injection of proinflammatory Cytokines, TNFα	BEP	Bovine coccygeal	Addition of TNFα resulted in a ctabolic shift, ↑ MMPs, ↑ ADAMTses	[115]
Mechanical Injury Models
Disc endplate fracture model, customized droptower to induce burst fractures in BEP	BEP, preserving 1/3 of a vertebral body	Rabbit	induced IVD degeneration much higher in burst fractures, ↑apoptosis, ↑MMPs, ↑interleukins in burst fractures, ↑LDH activity released to media	[35,47,120]
Single-ramp compression consistently cracks cartilaginous CEPs of healthy human IVDs, 5 % (non-injured) or 30 % (injured) strain	CEP	Bovine coccygeal	Mechanical injury resulted in about 40-50 % cell death viability in the NP, ↑Apoptosis, ↑inflammatory cytokines, ↑MMPS, ↑ADAMTses	[121]
Needle-stab or stab incision induced IVD degeneration	BEP	Bovine coccygeal	Needle stab models express ↑nitrite oxide (factor for stress), ↑LDH, stressed IVD releases factors that attract homing of MSCs	[74,87,116,133-135]