Interleukin-1 receptor antagonist deficient mice provide insights into pathogenesis of human intervertebral disc degeneration.
| Autor: | Phillips KL; Biomedical Research Centre, Faculty of Health and Wellbeing, Sheffield Hallam University, , Sheffield, UK., Jordan-Mahy N, Nicklin MJ, Le Maitre CL |
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| Jazyk: | angličtina |
| Zdroj: | Annals of the rheumatic diseases [Ann Rheum Dis] 2013 Nov; Vol. 72 (11), pp. 1860-7. Date of Electronic Publication: 2013 Feb 09. |
| DOI: | 10.1136/annrheumdis-2012-202266 |
| Abstrakt: | Objectives: Interleukin 1 (IL-1) is potentially important in the pathogenesis of intervertebral disc (IVD) degeneration; increasing production of matrix degradation enzymes and inhibiting matrix synthesis. Although IL-1 polymorphisms have been linked to increased risk of IVD degeneration, it is still unclear whether IL-1 drives IVD degeneration in vivo or is a secondary feature of degeneration. Here, we investigated whether IVD degeneration could be induced spontaneously by the removal of the natural inhibitor of IL-1 (IL-1 receptor antagonist) in mice that lack a functional IL-1rn gene. Methods: Histological staining and immunohistochemistry was performed on BALB/c IL-1rn(+/+) and IL-1rn(-/-) mice to examine degeneration and to localise and detect IL-1, matrix metalloproteinases (MMP)3, MMP7, a disintigrin and MMP with thrombospondin motifs (ADAMTS)4 protein production. In addition, IVD cells were isolated using collagenase and proliferation potential determined. Results: IL-1rn(-/-) knockout mice displayed typical features of human disc degeneration: loss of proteoglycan and normal collagen structure and increased expression of matrix degrading enzymes: MMP3; MMP7 and ADAMTS4. Histological grade of degeneration increased in IL-1rn(-/-) mice which was more evident within older mice. In addition IVD cells isolated from IL-1rn(-/-) mice displayed reduced proliferation potential. Conclusions: Here, we show that IL-1rn(-/-) mice develop spinal abnormalities that resemble characteristic features associated with human disc degeneration. The current evidence is consistent with a role for IL-1 in the pathogenesis of IVD degeneration. The imbalance between IL-1 and IL-1Ra which is observed during human IVD degeneration could therefore be a causative factor in the degeneration of the IVD, and as such, is an appropriate pharmaceutical target for inhibiting degeneration. |
| Databáze: | MEDLINE |
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