Association of macrophage metalloelastase MMP12 with intervertebral disc degeneration

Abstract

Background and objectives Low back pain is associated with intervertebral disc (IVD) degeneration, which usually starts from nucleus pulposus (NP). Matrix degradation, especially the decrease of proteoglycans, was reported in degenerated IVD. Metalloproteinases (MMPs) have known role for matrix degradation. Some MMPs have been shown to involve in IVD degeneration, including MMP2, MMP14 [1], MMP10 [2], MMP3 [3]. Evidence has suggested MMP12 (macrophage metalloelastase) is involved in many pathologic conditions and may play a pivotal role in the cascade activation of other MMPs [4, 5]. In IVD tissue, the detection of MMP12 has not been previously reported. In this study, we aimed to investigate the expression of MMP12 in IVD degeneration. Methods RNA was isolated from human NP cells derived from degenerated discs graded IV-V at the Schneiderman scale (n=4) and non-degenerated discs (scoliosis, n=3). Quantitative real-time PCR was performed to determine the expression of MMP12. GAPDH was used as the endogenous control. The protein expression of MMP12 was investigated by immunohistochemistry in mice aged from date of birth to 2 years old, and in rats at series of time points (pre-puncture and 2, 4, 6, 8 weeks post puncture) ith induced IVD degeneration by 25 gauge needle puncture. Results MMP12 was upregulated (5 fold) in cultured human degenerated NP cells compared to non-degenerated NP cells at mRNA level. Both AF and NP from human degenerated IVD had higher number of MMP12 expressing cells (4 fold) in contrast to AF and NP from human non-degenerated IVD. Growth and ageing in mice (P0 to 2 year) is associated with increasing MMP12 expression in the NP. In the induced degenerated IVD of rats, MMP12 expression was also increased by needle puncture, especially at the 8 weeks time point.

Conclusions Our results suggest the increase of MMP12 is an indicator of IVD degeneration. MMP12 is known to degrade aggrecan [6] and is involved in macrophage infiltration [7]. It is possible that the increase in MMP12 expression in degenerated NP is attributed by increased macrophage activities and is associated with the degradation of aggrecan. Further experiments will help to explain the source and role of MMP12 in the pathogenesis of IVD degeneration. References: 1. Rutges JP et al. 2008. 2. Richardson SM et al. 2009. 3. Yurube T et al. 2010. 4. Liang J et al. 2006. 5. Madala SK et al. 2010. 6. Durigova M et al. 2011. 7. England KA et al. 2011.