title: A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint.
abstract: Discoidin domain receptor 1 (DDR-1)-deficient mice exhibited a high incidence of osteoarthritis (OA) in the temporomandibular joint (TMJ) as early as 9 weeks of age. They showed typical histological signs of OA, including surface fissures, loss of proteoglycans, chondrocyte cluster formation, collagen type I upregulation, and atypical collagen fibril arrangements. Chondrocytes isolated from the TMJs of DDR-1-deficient mice maintained their osteoarthritic characteristics when placed in culture. They expressed high levels of runx-2 and collagen type I, as well as low levels of sox-9 and aggrecan. The expression of DDR-2, a key factor in OA, was increased. DDR-1-deficient chondrocytes from the TMJ were positively influenced towards chondrogenesis by a three-dimensional matrix combined with a runx-2 knockdown or stimulation with extracellular matrix components, such as nidogen-2. Therefore, the DDR-1 knock-out mouse can serve as a novel model for temporomandibular disorders, such as OA of the TMJ, and will help to develop new treatment options, particularly those involving tissue regeneration.
authors.affiliation: Oral Biology and Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, Robert Koch Straße 40, 37075, Goettingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schminke
authors.forename: Hayat
authors.initials: H
authors.lastname: Muhammad
authors.forename: Christa
authors.initials: C
authors.lastname: Bode
authors.forename: Boguslawa
authors.initials: B
authors.lastname: Sadowski
authors.forename: Regina
authors.initials: R
authors.lastname: Gerter
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gersdorff
authors.forename: Ralf
authors.initials: R
authors.lastname: Bürgers
authors.forename: Efrat
authors.initials: E
authors.lastname: Monsonego-Ornan
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000196:embryology / Q000473:pathology; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000070819:Discoidin Domain Receptor 1; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D011509:Proteoglycans / Q000172:deficiency; D034622:RNA Interference; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D038981:Receptors, Collagen / Q000378:metabolism; D015398:Signal Transduction; D013704:Temporomandibular Joint / Q000503:physiopathology*; D013705:Temporomandibular Joint Disorders / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; D011509:Proteoglycans; D034741:RNA, Small Interfering; D038981:Receptors, Collagen; C493716:Runx2 protein, mouse; C083249:Ddr1 protein, mouse; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases
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