{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:13:12Z","timestamp":1761718392254},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T00:00:00Z","timestamp":1430092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Congenital orofacial abnormalities are clinically seen in human syndromes with SHP2 germline mutations such as LEOPARD and Noonan syndrome. Recent studies demonstrate that SHP2-deficiency leads to skeletal abnormalities including scoliosis and cartilaginous benign tumor metachondromatosis, suggesting that growth plate cartilage is a key tissue regulated by SHP2. The role and cellular mechanism of SHP2 in the orofacial cartilage, however, remains unknown. Here, we investigated the postnatal craniofacial development by inducible disruption of Shp2 in chondrocytes. Shp2 conditional knockout (cKO) mice displayed severe deformity of the mandibular condyle accompanied by disorganized, expanded cartilage in the trabecular bone region, enhanced type X collagen, and reduced Erk production. Interestingly, the length of primary cilia, an antenna like organelle sensing environmental signaling, was significantly shortened, and the number of primary cilia was reduced in the cKO mice. The expression levels of intraflagellar transports (IFTs), essential molecules in the assembly and function of primary cilia, were significantly decreased. Taken together, lack of Shp2 in orofacial cartilage led to severe defects of ciliogenesis through IFT reduction, resulting in mandibular condyle malformation and cartilaginous expansion. Our study provides new insights into the molecular pathogenesis of SHP2-deficiency in cartilage and helps to understand orofacial and skeletal manifestations seen in patients with SHP2 mutations. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2541","type":"journal-article","created":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T12:17:29Z","timestamp":1430137049000},"page":"2028-2032","source":"Crossref","is-referenced-by-count":14,"title":["SHP2-Deficiency in Chondrocytes Deforms Orofacial Cartilage and Ciliogenesis in Mice"],"prefix":"10.1093","volume":"30","author":[{"given":"Nobuhiro","family":"Kamiya","sequence":"first","affiliation":[{"name":"Sports MedicineTenri UniversityTenriNaraJapan"},{"name":"Department of Orthopaedic SurgeryUniversity of Texas Southwestern Medical CenterDallasTXUSA"},{"name":"Center for Excellence in Hip DisordersTexas Scottish Rite Hospital for ChildrenDallasTXUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingling","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Histology and EmbryologyHarbin Medical UniversityHarbinChina"},{"name":"Department of PediatricsThe University of Texas Medical School at HoustonHoustonTXUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of PediatricsThe University of Texas Medical School at HoustonHoustonTXUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Kitami","sequence":"additional","affiliation":[{"name":"Department of PediatricsThe University of Texas Medical School at HoustonHoustonTXUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen-Sheng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Biological SciencesUniversity of CaliforniaSan Diego, La JollaCAUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of BiochemistryRush University Medical CenterChicagoILUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Graduate Program in Genes and DevelopmentThe University of Texas Graduate School of Biomedical Sciences at HoustonHoustonTXUSA"},{"name":"Department of PediatricsThe University of Texas Medical School at HoustonHoustonTXUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,4,27]]},"reference":[{"issue":"4","key":"2024020319010151500_jbmr2541-bib-0001","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0092-8674(00)80938-1","article-title":"Crystal structure of the tyrosine phosphatase 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