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To improve current subpar regenerative treatments, developmental mechanisms of AC should be clarified and, specifically, how its postnatal multizone organization is acquired. Primary cilia are cell surface organelles crucial for mammalian tissue morphogenesis. Although their importance for chondrocyte function is appreciated, their specific roles in postnatal AC morphogenesis remain unclear. To explore these mechanisms, we used a murine conditional loss-of-function approach (Ift88-flox) targeting joint-lineage progenitors (Gdf5Cre) and monitored postnatal knee AC development. Joint formation and growth up to juvenile stages were largely unaffected. However, mature AC (aged 2\u2009months) exhibited disorganized extracellular matrix, decreased aggrecan and collagen II due to reduced gene expression (not increased catabolism), and marked reduction of AC modulus by 30%\u201350%. In addition, and unexpectedly, we discovered that tidemark patterning was severely disrupted, as was hedgehog signaling, and exhibited specificity based on regional load-bearing functions of AC. Interestingly, Prg4 expression was markedly increased in highly loaded sites in mutants. Together, our data provide evidence that primary cilia orchestrate postnatal AC morphogenesis including tidemark topography, zonal matrix composition, and ambulation load responses. \u00a9 2022 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4506","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T07:57:15Z","timestamp":1642751835000},"page":"1097-1116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9952-4474","authenticated-orcid":false,"given":"Danielle","family":"Rux","sequence":"first","affiliation":[{"name":"Translational Research Program in Pediatric Orthopaedics Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Helbig","sequence":"additional","affiliation":[{"name":"Translational Research Program in Pediatric Orthopaedics Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7812-3524","authenticated-orcid":false,"given":"Biao","family":"Han","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science and Health Systems Drexel University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Cortese","sequence":"additional","affiliation":[{"name":"Translational Research Program in Pediatric Orthopaedics Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-6820","authenticated-orcid":false,"given":"Eiki","family":"Koyama","sequence":"additional","affiliation":[{"name":"Translational Research Program in Pediatric Orthopaedics Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4180-1288","authenticated-orcid":false,"given":"Lin","family":"Han","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science and Health Systems Drexel University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-4942","authenticated-orcid":false,"given":"Maurizio","family":"Pacifici","sequence":"additional","affiliation":[{"name":"Translational Research Program in Pediatric Orthopaedics Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"2024012713574237200_jbmr4506-bib-0001","volume-title":"Physiology of Synovial Joints and Articular Cartilage","author":"Mow","year":"2001","edition":"3rd ed"},{"issue":"1","key":"2024012713574237200_jbmr4506-bib-0002","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11914-014-0247-7","article-title":"Synovial joints: from development to homeostasis","volume":"13","author":"Longobardi","year":"2015","journal-title":"Curr Osteoporos Rep"},{"key":"2024012713574237200_jbmr4506-bib-0003","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2016.10.005","article-title":"Articular cartilage and joint development from embryogenesis to adulthood","volume":"62","author":"Decker","year":"2017","journal-title":"Semin Cell Dev 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