{"data":{"id":"10.25384/sage.c.4127564","type":"dois","attributes":{"doi":"10.25384/sage.c.4127564","prefix":"10.25384","suffix":"sage.c.4127564","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"A.W. Rogers","affiliation":[],"nameIdentifiers":[]},{"name":"S.E. Cisewski","affiliation":[],"nameIdentifiers":[]},{"name":"C.B. Kern","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"The Zonal Architecture of the Mandibular Condyle Requires ADAMTS5"}],"publisher":"Figshare","container":{},"publicationYear":2018,"subjects":[{"subject":"110599 Dentistry not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"91299 Materials Engineering not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Materials engineering","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2018-06-08","dateType":"Created"},{"date":"2018-06-08","dateType":"Updated"},{"date":"2018","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1177/0022034518777751","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"CC BY 4.0","rightsUri":"https://creativecommons.org/licenses/by/4.0"}],"descriptions":[{"description":"Temporomandibular joint (TMJ) osteoarthritis (TMJOA) disrupts extracellular matrix (ECM) homeostasis, leading to cartilage degradation. Upregulated a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)–5 leads to cleavage of its substrate aggrecan (Acan) and is considered a hallmark of TMJOA. However, most research on ADAMTS5-Acan turnover has focused on hyaline cartilage, not fibrocartilage, which comprises the TMJ. The mandibular condylar cartilage (MCC) of the TMJ is organized in zones, and chondrocytes are arranged in axial rows, yet the molecular mechanisms required to generate the MCC zonal architecture have not been elucidated. Here, we test the hypothesis that ADAMTS5 is required for development of the TMJ MCC. \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e+/+\u003c/sup\u003e and \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e–/–\u003c/sup\u003e murine TMJs were harvested at postnatal day 7 (P7), P21, 2 mo, and 6 mo of age; histomorphometrics indicated increased ECM. Immunohistochemistry and Western blots demonstrated the expanded ECM correlated with increased Acan localization in \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e–/–\u003c/sup\u003e compared to \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e+/+\u003c/sup\u003e. Cell volume was also decreased in the MCC of \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e–/–\u003c/sup\u003e due to both a reduction in cell size and less mature hypertrophic chondrocytes. Analysis of chondrogenic maturation markers by quantitative real-time polymerase chain reaction indicated \u003ci\u003eCol2a1\u003c/i\u003e, \u003ci\u003eCol10a1\u003c/i\u003e, and \u003ci\u003eSox9\u003c/i\u003e were significantly reduced in \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e–/–\u003c/sup\u003e MCC compared to that of \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e+/+\u003c/sup\u003e. The older (6 mo) \u003ci\u003eAdamts5\u003c/i\u003e\u003csup\u003e–/–\u003c/sup\u003e MCC exhibited changes in chondrogenic cell arrangements, including clustering and chondrogenic atrophy, that correlated with early stages of TMJOA using modified Mankin scoring. These data indicate a potentially novel and critical role of ADAMTS5 for maturation of hypertrophic chondrocytes and establishment of the zonal architecture that, when disrupted, may lead to early onset of TMJOA.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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