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However, there is no direct genetic evidence for the role of Ihh in OA, because mice with cartilage or other tissue-specific deletion of the <jats:italic>Ihh<\/jats:italic> gene die shortly after birth. We evaluated the role of Ihh <jats:italic>in vivo<\/jats:italic> via a Cre-loxP-mediated approach to circumvent the early death caused by <jats:italic>Ihh<\/jats:italic> deficiency.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>To evaluate the role of Ihh in OA development, <jats:italic>Ihh<\/jats:italic> was specifically deleted in murine cartilage using an <jats:italic>Ihh<\/jats:italic> conditional deletion construct (<jats:italic>Col2a1-CreER<\/jats:italic><jats:sup>\n                              <jats:italic>T2<\/jats:italic>\n                           <\/jats:sup>; Ihh<jats:sup>fl\/fl<\/jats:sup>). The extent of cartilage degradation and OA progression after <jats:italic>Ihh<\/jats:italic> deletion was assessed by histological analysis, immunohistochemistry, real-time PCR and <jats:italic>in vivo<\/jats:italic> fluorescence molecular tomography (FMT) 2 months after OA was induced by partial medial meniscectomy. The effect of Ihh signaling on cartilage was compared between <jats:italic>Ihh<\/jats:italic>-deleted mice and their control littermates.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Only mild OA changes were observed in <jats:italic>Ihh<\/jats:italic>-deleted mice, while control mice displayed significantly more cartilage damage. Typical OA markers such as type X collagen and MMP-13 were decreased in <jats:italic>Ihh<\/jats:italic>-deleted mice. <jats:italic>In vivo<\/jats:italic> FMT demonstrated decreased cathepsins and MMP activity in knee joints of animals with deletion of <jats:italic>Ihh<\/jats:italic>.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>These findings support the protective role of <jats:italic>Ihh<\/jats:italic> deletion in surgically induced OA. Thus, our findings suggest the potential to develop new therapeutic strategies that can prevent and treat OA by inhibiting Ihh signaling in chondrocytes.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4437","type":"journal-article","created":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T18:35:41Z","timestamp":1389810941000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreER\n                     \n                        T2\n                     ; Ihhfl\/fl mice"],"prefix":"10.1186","volume":"16","author":[{"given":"Jingming","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Lanske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braden C","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Terek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,1,15]]},"reference":[{"key":"4104_CR1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.cger.2010.03.002","volume":"26","author":"RF Loeser","year":"2010","unstructured":"Loeser RF: Age-related changes in the musculoskeletal system and the development of osteoarthritis. 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