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It is not clear whether the two types of osteoarthritis share common mechanisms. We found that miR\u2010146a, a micro\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    \u2010associated with inflammation, is activated by cyclic load in the physiological range but suppressed by mechanical overload in human articular chondrocytes. Furthermore, miR\u2010146a expression is decreased in the\n                    <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\n                    lesions of human articular cartilage. To understand the role of miR\u2010146a in osteoarthritis, we systemically characterized mice in which miR\u2010146a is either deficient in whole body or overexpressed in chondrogenic cells specifically. miR\u2010146a\u2010deficient mice develop early onset of\n                    <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\n                    characterized by cartilage degeneration, synovitis, and osteophytes. Conversely, miR\u2010146a chondrogenic overexpressing mice are resistant to aging\u2010associated\n                    <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\n                    . Loss of miR\u2010146a exacerbates articular cartilage degeneration during\n                    <jats:styled-content style=\"fixed-case\">PTOA<\/jats:styled-content>\n                    , while chondrogenic overexpression of miR\u2010146a inhibits\n                    <jats:styled-content style=\"fixed-case\">PTOA<\/jats:styled-content>\n                    . Thus, miR\u2010146a inhibits both\n                    <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">PTOA<\/jats:styled-content>\n                    in mice, suggesting a common protective mechanism initiated by miR\u2010146a. miR\u2010146a suppresses\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u20101\u03b2 of catabolic factors, and we provide evidence that miR\u2010146a directly inhibits Notch1 expression. Therefore, such inhibition of Notch1 may explain suppression of inflammatory mediators by miR\u2010146a. Chondrogenic overexpression of miR\u2010146a or intra\u2010articular administration of a Notch1 inhibitor alleviates\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u20101\u03b2\u2010induced catabolism and rescues joint degeneration in miR\u2010146a\u2010deficient mice, suggesting that miR\u2010146a is sufficient to protect\n                    <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\n                    pathogenesis by inhibiting Notch signaling in the joint. Thus, miR\u2010146a may be used to counter both aging\u2010associated\n                    <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\n                    and mechanical injury\u2010\/inflammation\u2010induced\n                    <jats:styled-content style=\"fixed-case\">PTOA<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/acel.12752","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T02:15:00Z","timestamp":1521944100000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Evidence that miR\u2010146a attenuates aging\u2010 and trauma\u2010induced osteoarthritis by inhibiting Notch1,\n                    <scp>IL<\/scp>\n                    \u20106, and\n                    <scp>IL<\/scp>\n                    \u20101 mediated catabolism"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-0632","authenticated-orcid":false,"given":"Ying\u2010Jie","family":"Guan","sequence":"first","affiliation":[{"name":"Bone and Joint Research Center The First Affiliated Hospital and Frontier Institute of Science and Technology Xi'an JiaoTong University Xi'an China"},{"name":"Cell and Molecular Biology Laboratory Department of Orthopaedics Alpert Medical School of Brown University\/Rhode Island Hospital Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center The First Affiliated Hospital and Frontier Institute of Science and Technology Xi'an JiaoTong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Affiliated Hospital of Medical College of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Du","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Laboratory Department of Orthopaedics Alpert Medical School of Brown University\/Rhode Island Hospital Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ding","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Laboratory Department of Orthopaedics Alpert Medical School of Brown University\/Rhode Island Hospital Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Gao","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Laboratory Department of Orthopaedics Alpert Medical School of Brown University\/Rhode Island Hospital Providence RI 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