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Eur Spine J. 2019 Nov 22. doi: 10.1007/s00586-019-06227-3. [Epub ahead of print]

Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc.

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Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093, Zurich, Switzerland.
Prodorso Spine Center, Walchestrasse 15, 8006, Zurich, Switzerland.
Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Warener Str. 7, 12683, Berlin, Germany.
Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093, Zurich, Switzerland.
Department of Biomedical Engineering, Rochester Institute of Technology (RIT), 160 Lomb Memorial Drive Bldg. 73, Rochester, NY, 14623, USA.
Schön Clinic Munich Harlaching, Spine Center, Academic Teaching Hospital and Spine Research Institute of the Paracelsus Medical University Salzburg (Austria), Harlachinger Str. 51, 81547, Munich, Germany.



Hyaluronic acid plays an essential role in water retention of the intervertebral disc (IVD) and thus provides flexibility and shock absorbance in the spine. Hyaluronic acid gets degraded by hyaluronidases (HYALs), and some of the resulting fragments were previously shown to induce an inflammatory and catabolic response in human IVD cells. However, no data currently exist on the expression and activity of HYALs in IVD health and disease.


Gene expression, protein expression and activity of HYALs were determined in human IVD biopsies with different degrees of degeneration (n = 50 total). Furthermore, freshly isolated human IVD cells (n = 23 total) were stimulated with IL-1β, TNF-α or H2O2, followed by analysis of HYAL-1, HYAL-2 and HYAL-3 gene expression.


Gene expression of HYAL-1 and protein expression of HYAL-2 significantly increased in moderate/severe disc samples when compared to samples with no or low IVD degeneration. HYAL activity was not significantly increased due to high donor-donor variation, but seemed overall higher in the moderate/severe group. An inflammatory environment, as seen during IVD disease, did not affect HYAL-1, HYAL-2 or HYAL-3 expression, whereas exposure to oxidative stress (100 µM H2O2) upregulated HYAL-2 expression relative to untreated controls.


Although HYAL-1, HYAL-2 and HYAL-3 are all expressed in the IVD, HYAL-2 seems to have the highest pathophysiological relevance. Nonetheless, further studies will be needed to comprehensively elucidate its significance and to determine its potential as a therapeutic target. These slides can be retrieved under Electronic Supplementary Material.


Degenerative disc disease; Extracellular matrix; Glycosaminoglycan; Hyaluronic acid; Inflammation; Oxidative stress


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