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By virtue of their small size, chemokines support the crosstalk between cartilage and other joint compartments and contribute to immune cell chemotaxis in osteoarthritis (OA). Here we employed shRNA retroviruses to stably and efficiently ablate the expression of each IKK in primary OA chondrocytes to determine their individual contributions for monocyte chemotaxis in response to chondrocyte conditioned media. Both IKK\u03b1 and IKK\u03b2 KDs blunted both the monocyte chemotactic potential and the protein levels of CCL2\/MCP-1, the chemokine with the highest concentration and the strongest association with monocyte chemotaxis. These findings were mirrored by gene expression analysis indicating that the lowest levels of CCL2\/MCP-1 and other monocyte-active chemokines were in IKK\u03b1KD cells under both basal and IL-1\u03b2 stimulated conditions. We find that in their response to IL-1\u03b2 stimulation IKK\u03b1KD primary OA chondrocytes have reduced levels of phosphorylated NFkappaB p65pSer536 and H3pSer10. Confocal microscopy analysis revealed co-localized p65 and H3pSer10 nuclear signals in agreement with our findings that IKK\u03b1KD effectively blunts their basal level and IL-1\u03b2 dependent increases. Our results suggest that IKK\u03b1 could be a novel OA disease target.<\/jats:p>","DOI":"10.1038\/s41598-021-01063-2","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T11:37:43Z","timestamp":1636025863000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Basal and IL-1\u03b2 enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKK\u03b1 and IKK\u03b2 NF-\u03baB activating kinases"],"prefix":"10.1038","volume":"11","author":[{"given":"Eleonora","family":"Olivotto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Minguzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"D\u2019Adamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Astolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spartaco","family":"Santi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Uguccioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Marcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Borz\u00ec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"1063_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1002\/art.40355","volume":"70","author":"SR Jafarzadeh","year":"2018","unstructured":"Jafarzadeh, S. 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