ADAMTS5 is required for normal trabeculated bone development in the mandibular condyle

Determine the role of the extracellular matrix protease ADAMTS5 in development of the trabeculated bone of the mandibular condyle. The mandibular condyles of wild type and mice deficient in the protease ADAMTS5 were examined for histopathology with Safranin O staining. Microcomputed tomography was p...

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Bibliographic Details
Published in:	Osteoarthritis and cartilage Vol. 29; no. 4; pp. 547 - 557
Main Authors:	Rogers-DeCotes, A.W., Porto, S.C., Dupuis, L.E., Kern, C.B.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-04-2021
Subjects:	ADAMTS ADAMTS5 Protein - genetics ADAMTS5 Protein - physiology Animals Bone Cancellous Bone - diagnostic imaging Cancellous Bone - growth & development Cancellous Bone - metabolism Chondrocytes - metabolism Extracellular matrix Mandibular condyle Mandibular Condyle - diagnostic imaging Mandibular Condyle - growth & development Mandibular Condyle - metabolism Matrix Metalloproteinase 13 - metabolism Mesenchymal Stem Cells - metabolism Mice Mice, Knockout Osteoblasts - metabolism Osteocalcin - metabolism Temporomandibular joint (TMJ) Versicans - metabolism X-Ray Microtomography Zinc Finger Protein GLI1 - metabolism μCT ADAMTS Mandibular condyle MCC ECM TMJ Acan ADAMTS5 MMP Vcan Temporomandibular joint (TMJ) Extracellular matrix Bone
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Summary:	Determine the role of the extracellular matrix protease ADAMTS5 in development of the trabeculated bone of the mandibular condyle. The mandibular condyles of wild type and mice deficient in the protease ADAMTS5 were examined for histopathology with Safranin O staining. Microcomputed tomography was performed to analyze the developing bone of the mandibular condyle. RNAscope and immunohistochemistry were utilized to investigate cell type and extracellular matrix expression. Mice deficient in Adamts5, (Adamts5tm1Dgen/J) exhibit an increase in trabecular separation (n = 37 wild type; n = 27: P < 0.0001) and reduction of trabecular thickness P = 0.0116 and bone volume fraction P = 0.0869 in the mandibular condylar head compared to wild type littermates. The altered bone parameters were more pronounced in male Adamts5−/− mice compared to female Adamts5−/− mice (TbSp; P = 0.03). Adamts5 was co-expressed with versican and Gli1 in mesenchymal, stem-like cells in the transition zone where the trabeculated bone is adjacent to mature hypertrophic chondrocytes. Loss of Adamts5 caused a reduction of Bglap expressing osteoblasts throughout mandibular condylar development and in young adult mice. The protease Mmp13, that is involved in mineralization and is expressed by hypertrophic chondrocytes and osteoblasts, was reduced in the mandibular condyle of Adamts5 deficient mice. This is the first report of a novel and critical role for Adamts5 in bone formation within the mandibular condyle of the temporomandibular joint. These data indicate Adamts5 may be required in the transdifferentiation of hypertrophic chondrocytes to osteoblasts during trabecular bone formation in development of the mandibular condyle.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Contributions: AWR was involved in the design and acquisition and analysis of data, performed statistical studies, drafting of the article and approved the final submitted version. SCP facilitated the conception of the study, acquired data, performed statistical studies, revised a manuscript draft and approved the final submission. LED was involved in the design of the experiments, generated the models and provided intellectual content and approved the final version for submission. CBK was involved in the conception of the study, interpretation of the data, writing the manuscript and funding of the study as well as approval of the final submission.
ISSN:	1063-4584 1522-9653 1522-9653
DOI:	10.1016/j.joca.2021.01.005