Expression of Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Interleukins in Vertebral Cartilage Endplate.

OBJECTIVE: Turnover of cartilage endplate extracellular matrix (ECM) may play an important role in disc degeneration and low back pain (LBP). However, the expression pattern of pro-inflammatory factors, matrix metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) in the cartilage endplates (CEP) of intervertebral discs (IVD) is not understood. We aimed to examine the transcriptional levels of MMP, TIMP, and interleukins (IL), and the correlations between them.

METHODS: Thirty degenerated cartilage endplate samples from patients with LBP who underwent lumbar fusion surgery were included in the degenerated group. Ten patients without LBP history who underwent lumbar surgery because of vertebral burst fractures were included in the control group. The degenerative severity of the samples was evaluated by MRI, and hematoxylin-eosin and safranin O-fast green (SO-FG) staining. Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3, IL-1α, IL-1β, and IL-6. The correlations between the levels of these genes were tested using Spearman's rho test.

RESULTS: Hematoxylin-eosin and SO-FG staining confirmed a decrease in cell number and proteoglycans in the degenerated cartilage endplate. MRI showed significant signal changes in degenerated cartilage endplates. Patients in the degenerated group showed a higher rate of endplate Modic changes when compared with the control group. MMP-3, MMP-9, TIMP-3, IL-1α, and IL-1β were elevated with statistical significance, while MMP-1, MMP-13, TIMP-1, TIMP-2, and IL-6 were changed without statistical significance or remained unchanged. Expression of MMP-3 was positively correlated with IL-1α (Spearman coefficient, 0.486; P < 0.05); expression of TIMP-3 was positively correlated with MMP-9, IL-1α, and IL-1β (Spearman coefficient, 0.577, 0.407, and 0.571, respectively; P < 0.05).

CONCLUSION: MMP-3, MMP-9, TIMP-3, IL-1α, and IL-1β may play a role in the process of cartilage endplate degeneration. MMP-3 may be regulated by IL-1α, and TIMP-3 might be associated with MMP-9 and regulated by IL-1α and IL-1β.