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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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Gene expression, protein expression and activity of HYALs were determined in human IVD biopsies with different degrees of degeneration (<jats:italic>n<\/jats:italic>\u2009=\u200950 total). Furthermore, freshly isolated human IVD cells (<jats:italic>n<\/jats:italic>\u2009=\u200923 total) were stimulated with IL-1\u03b2, TNF-\u03b1 or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, followed by analysis of HYAL-1, HYAL-2 and HYAL-3 gene expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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\u2013donor 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\u00a0\u00b5M H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) upregulated HYAL-2 expression relative to untreated controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphic abstract<\/jats:title>\n                <jats:p>These slides can be retrieved under Electronic Supplementary Material. <\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00586-019-06227-3","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T17:02:31Z","timestamp":1574442151000},"page":"605-615","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc"],"prefix":"10.1007","volume":"29","author":[{"given":"Olga","family":"Krupkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Greutert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Boos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Lemcke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Liebscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-4629","authenticated-orcid":false,"given":"Karin","family":"Wuertz-Kozak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"6227_CR1","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1016\/j.bbagen.2014.07.013","volume":"1840","author":"SS Sivan","year":"2014","unstructured":"Sivan SS, Wachtel E, Roughley P (2014) Structure, function, aging and turnover of aggrecan in the intervertebral disc. 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