{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:03:10Z","timestamp":1781899390528,"version":"3.54.5"},"reference-count":65,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T00:00:00Z","timestamp":1576108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010224","name":"Philosophy and Social Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2018JJ2636"],"award-info":[{"award-number":["2018JJ2636"]}],"id":[{"id":"10.13039\/501100010224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010224","name":"Philosophy and Social Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2016JJ3160"],"award-info":[{"award-number":["2016JJ3160"]}],"id":[{"id":"10.13039\/501100010224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874030"],"award-info":[{"award-number":["81874030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:p>The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up\u2010regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix\u2010degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of <jats:italic>HH<\/jats:italic> gene is not an option for OA treatment in humans because it is not possible to delete <jats:italic>HH<\/jats:italic> in larger animals. Efficient knockdown of <jats:italic>HH<\/jats:italic> achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.<\/jats:p>","DOI":"10.1002\/cbf.3448","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T01:03:43Z","timestamp":1576199023000},"page":"122-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Functional role of hedgehog pathway in osteoarthritis"],"prefix":"10.1002","volume":"38","author":[{"given":"Wen\u2010feng","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8364-9988","authenticated-orcid":false,"given":"Ang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2016.12.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.01.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9917-9"},{"key":"e_1_2_9_5_1","first-page":"356","article-title":"T cells in osteoarthritis: alterations and beyond","volume":"8","author":"Li YS","year":"2017","journal-title":"Front Immunol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030674"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.44"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000351"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2015.06.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12362"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2017.1360353"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7669"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2018.2756"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7110208"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21482"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2984"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-017-0191-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.28089"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-11-2"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.833"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.02.010"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.095141"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082279"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8020098"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00564.2007"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120154"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17060857"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers7040880"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5838"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.08.003"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-016-0509-3"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.05.007"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2008.00430.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S139639"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.043281"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.069492"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0891-z"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21372"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139740"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25761"},{"issue":"5","key":"e_1_2_9_41_1","first-page":"876","article-title":"Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions","volume":"32","author":"Tchetina EV","year":"2005","journal-title":"J Rheumatol"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.12.016"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.03.010"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20584"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2055"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39337"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2009.04.009"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.08.009"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4437"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203248"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-274944"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80205"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.910983"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-1895-x"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.143959"},{"key":"e_1_2_9_56_1","first-page":"789","article-title":"The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation","volume":"15","author":"Deng A","year":"2018","journal-title":"Exp Ther Med"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.03.022"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150363"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar148"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep10290"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20656"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn076"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00188"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/jfb3010079"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2617"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.23674"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcbf.3448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.3448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbf.3448","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.3448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T23:08:33Z","timestamp":1760051313000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.3448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,12]]},"references-count":65,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/cbf.3448"],"URL":"https:\/\/doi.org\/10.1002\/cbf.3448","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,12]]},"assertion":[{"value":"2019-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}