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Kazezian, Z., Li, Z., Alini, M., Grad, S. and Pandit, A.
Acta Biomateriala
Injectable Hyaluronic Acid Down-regulates Interferon Signalling Molecules, IGFBP3 and IFIT3 in the Bovine Intervertebral Dis
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Low back pain which is a major cause of disability for people aged between 20 and 50 years imposes a serious socioeconomic burden. The current focus of regenerative medicine is on identifying molecular markers to facilitate the design of targeted therapeutics. Previously, we have demonstrated that expression of the anti-proliferative interferon induced protein with tetratricopeptide repeats 3 (IFIT3) and proapoptotic insulin-like growth factor-binding protein-3 (IGFBP3), are upregulated as downstream targets of the inflammatory cytokine interferon α (IFNα) signalling pathway in the human annulus fibrosus (AF). Here, we hypothesized that injection of hyaluronic acid (HA) would have an anti-inflammatory and matrix modulatory effect on injured and IFNα2β inflamed bovine intervertebral discs (IVD). Discs with an AF defect and challenged with IFNα2β were used in a bovine IVD organ culture model to test the effect of HA on the IFNα2β pathway, as well as the matrix proteins aggrecan and collagen I. qRT-PCR was used to assess the gene expression of IFNα2β signalling molecules. Additionally, immunostaining was used to measure protein expression. Our results show that HA treatment significantly down-regulates IFNAR1, IFNAR2, STAT1/2, JAK1, IFIT3 and IGFBP3 mRNA expression in the inflamed groups. Protein analysis confirmed the PCR results. In the extracellular matrix, aggrecan and collagen I were up-regulated while ADAMTS4 was down-regulated upon treatment of the injured and inflamed discs with HA. Hence, HA demonstrates both an antiinflammatory role, resulting in the down-regulation of IFIT3 and IGFBP3 in the AF, and a matrix modulatory effect by up-regulating aggrecan and collagen I expression.
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