{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:24:58Z","timestamp":1791667498397,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T00:00:00Z","timestamp":1422403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hedgehog (HH) signaling has recently been associated with cartilage degradation in osteoarthritis (OA). Because interleukin\u20101\u03b2 (IL\u20101\u03b2) has been implicated as a principal instigator of OA, we sought to determine whether IL\u20101\u03b2 induces the expression of sonic HH (SHH) and its regulation by microRNAs (miRNAs) in human chondrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Expression of SHH protein in human OA cartilage and in an animal model of OA was determined by immunohistochemical analysis and immunofluorescence analysis, respectively. Gene and protein expression in IL\u20101\u03b2\u2013 or SHH\u2010stimulated OA chondrocytes was determined by TaqMan assays and Western blotting, respectively. The effect of overexpression of miRNA\u2010602 (miR\u2010602) and miR\u2010608 or their antagomirs on SHH expression was evaluated by transient transfection of human chondrocytes and HEK 293 cells. The role of signaling pathways was evaluated using small molecule inhibitors. Binding of miRNAs with the putative seed sequence in SHH messenger RNA (mRNA) was validated using a luciferase reporter assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Expression of SHH, patched 1, Gli\u20101, HH\u2010interacting protein, matrix metalloproteinase 13 (MMP\u201013), and Col\u03b11(X) was high in damaged OA cartilage. In damaged cartilage and in IL\u20101\u03b2\u2013stimulated OA chondrocytes, expression of SHH was inversely correlated with expression of miR\u2010608. Cotransfection of OA chondrocytes with miR\u2010608 or miR\u2010602 mimic inhibited reporter activity, and mutation of the miRNA seed sequences abolished the repression of reporter activity. Overexpression of miR\u2010602 or miR\u2010608 inhibited the expression of SHH mRNA and protein, and this was abrogated by antagomirs. Stimulation with recombinant human SHH protein up\u2010regulated MMP\u201013 expression, and inhibition of HH signaling blocked MMP\u201013 expression in OA chondrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MiR\u2010602 and miR\u2010608 are important posttranscription regulators of SHH expression in OA chondrocytes, and their suppression by IL\u20101\u03b2 may contribute to the enhanced expression of SHH and MMP\u201013 in OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.38952","type":"journal-article","created":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T14:22:36Z","timestamp":1415629356000},"page":"423-434","source":"Crossref","is-referenced-by-count":60,"title":["MicroRNA\u2010602 and MicroRNA\u2010608 Regulate Sonic Hedgehog Expression via Target Sites in the Coding Region in Human Chondrocytes"],"prefix":"10.1002","volume":"67","author":[{"given":"Nahid","family":"Akhtar","sequence":"first","affiliation":[{"name":"Northeast Ohio Medical University Rootstown"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad S.","family":"Makki","sequence":"additional","affiliation":[{"name":"Northeast Ohio Medical University Rootstown"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq M.","family":"Haqqi","sequence":"additional","affiliation":[{"name":"Northeast Ohio Medical University 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