{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:27:37Z","timestamp":1790836057594,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is associated with cartilage breakdown, brought about by ADAMTS-5 mediated aggrecan degradation followed by MMP-derived aggrecan and type II collagen degradation. We investigated a novel anti-ADAMTS-5 inhibiting Nanobody\u00ae (M6495) on cartilage turnover ex vivo. Bovine cartilage (BEX, n = 4), human osteoarthritic - (HEX, n = 8) and healthy\u2014cartilage (hHEX, n = 1) explants and bovine synovium and cartilage were cultured up to 21 days in medium alone (w\/o), with pro-inflammatory cytokines (oncostatin M (10 ng\/mL) + TNF\u03b1 (20 ng\/mL) (O + T), IL-1\u03b1 (10 ng\/mL) or oncostatin M (50 ng\/mL) + IL-1\u03b2 (10 ng\/mL)) with or without M6495 (1000\u22120.46 nM). Cartilage turnover was assessed in conditioned medium by GAG (glycosaminoglycan) and biomarkers of ADAMTS-5 driven aggrecan degradation (huARGS and exAGNxI) and type II collagen degradation (C2M) and formation (PRO-C2). HuARGS, exAGNxI and GAG peaked within the first culture week in pro-inflammatory stimulated explants. C2M peaked from day 14 by O + T and day 21 in co-culture experiments. M6495 dose dependently decreased huARGS, exAGNxI and GAG after pro-inflammatory stimulation. In HEX C2M was dose-dependently reduced by M6495. M6495 showed no effect on PRO-C2. M6495 showed cartilage protective effects by dose-dependently inhibiting ADAMTS-5 mediated cartilage degradation and inhibiting overall cartilage deterioration in ex vivo cartilage cultures.<\/jats:p>","DOI":"10.3390\/ijms21175992","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T21:13:42Z","timestamp":1597958022000},"page":"5992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The Anti-ADAMTS-5 Nanobody\u00ae M6495 Protects Cartilage Degradation Ex Vivo"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-8422","authenticated-orcid":false,"given":"Anne Sofie","family":"Siebuhr","sequence":"first","affiliation":[{"name":"ImmunoScience, Nordic Bioscience Biomarkers and Research, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Werkmann","sequence":"additional","affiliation":[{"name":"Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-C.","family":"Bay-Jensen","sequence":"additional","affiliation":[{"name":"ImmunoScience, Nordic Bioscience Biomarkers and Research, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian S.","family":"Thudium","sequence":"additional","affiliation":[{"name":"ImmunoScience, Nordic Bioscience Biomarkers and Research, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Asser","family":"Karsdal","sequence":"additional","affiliation":[{"name":"ImmunoScience, Nordic Bioscience Biomarkers and Research, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikte","family":"Serruys","sequence":"additional","affiliation":[{"name":"Ablynx, A Sanofi Company, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ladel","sequence":"additional","affiliation":[{"name":"Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1110\/ps.073287008","article-title":"Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5","volume":"17","author":"Mosyak","year":"2008","journal-title":"Protein Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","article-title":"Proteases involved in cartilage matrix degradation in osteoarthritis","volume":"1824","author":"Troeberg","year":"2012","journal-title":"Biochim. 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