{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:11:20Z","timestamp":1777486280744,"version":"3.51.4"},"reference-count":26,"publisher":"SAGE Publications","issue":"2_suppl","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP19\/00172"],"award-info":[{"award-number":["CP19\/00172"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00409"],"award-info":[{"award-number":["PI17\/00409"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000783","name":"Research Executive Agency","doi-asserted-by":"publisher","award":["Project number 734899"],"award-info":[{"award-number":["Project number 734899"]}],"id":[{"id":"10.13039\/501100000783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["CP19\/00172"],"award-info":[{"award-number":["CP19\/00172"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI17\/00409"],"award-info":[{"award-number":["PI17\/00409"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010556","name":"Conseller\u00eda de Econom\u00eda, Emprego e Industria, Xunta de Galicia","doi-asserted-by":"publisher","award":["IN607B2019\/10"],"award-info":[{"award-number":["IN607B2019\/10"]}],"id":[{"id":"10.13039\/501100010556","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["CARTILAGE"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is an age-related biomechanical and low-grade inflammometabolic disease of the joints and one of the costliest and disabling forms of arthritis. Studies on matrix-degrading enzymes such as metalloproteases, which are implicated in the increased catabolism of extracellular matrix, are of paramount relevance. DKK3 is a member of DKK family and is best known for its role in cancer. Although there is some information about the participation of DKK3 in cartilage pathophysiology and on metalloproteases regulation, in particular, little is known about DKK3 signaling mechanisms. Thus, the aim of this study is to explore how DKK3 regulates matrix metalloproteinase-13 (MMP-13) expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Gene, protein expression and protein phosphorylation in primary human chondrocytes and ATDC5 mouse cells were assessed by RT-qPCR and Western blot analysis. Further studies on DKK3 activity were performed by targeting DKK3 gene with a specific siRNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DKK3 expression was found to be higher in OA human chondrocytes than healthy cells, being its expression decreased in interleukin-1\u03b1 (IL-1\u03b1)-stimulated cells. DKK3 knockdown increased the induction of MMP-13 elicited by IL-1\u03b1 in human and mouse chondrocytes and after the analysis of different signalling pathways, we observed that NF-\u03baB pathway was involved in the regulation of MMP-13 expression by DKK3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Herein we have demonstrated, for the first time, that DKK3 gene silencing exacerbated NF-\u03baB activation, resulting in an increased IL-1\u03b1-driven induction of MMP-13. Our results further confirm that DKK3 may play a protective role in OA by attenuating NF-\u03baB activation and the subsequent production of metalloproteases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1947603520933328","type":"journal-article","created":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T02:17:02Z","timestamp":1592014622000},"page":"925S-934S","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Dickkopf-3 (DKK3) Signaling in IL-1\u03b1-Challenged Chondrocytes: Involvement of the NF-\u03baB Pathway"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-479X","authenticated-orcid":false,"given":"Javier","family":"Conde","sequence":"first","affiliation":[{"name":"SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigaci\u00f3n Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morena","family":"Scotece","sequence":"additional","affiliation":[{"name":"SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigaci\u00f3n Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodolfo","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Musculoskeletal Pathology Laboratory, Institute IDIS, Santiago University Clinical Hospital, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Lago","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology Group, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigaci\u00f3n Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel Angel","family":"Gonzalez-Gay","sequence":"additional","affiliation":[{"name":"Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria and IDIVAL, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Pino","sequence":"additional","affiliation":[{"name":"SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigaci\u00f3n Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Mobasheri","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, 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