A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint

Boris Schminke; Hayat Muhammad; Christa Bode; Boguslawa Sadowski; Regina Gerter; Nikolaus Gersdorff; Ralf Bürgers; Efrat Monsonego-Ornan; Vicki Rosen; Nicolai Miosge

doi:10.1007/s00018-013-1436-8

A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint

Cell Mol Life Sci. 2014 Mar;71(6):1081-96. doi: 10.1007/s00018-013-1436-8. Epub 2013 Aug 4.

Authors

Boris Schminke¹, Hayat Muhammad, Christa Bode, Boguslawa Sadowski, Regina Gerter, Nikolaus Gersdorff, Ralf Bürgers, Efrat Monsonego-Ornan, Vicki Rosen, Nicolai Miosge

Affiliation

¹ Oral Biology and Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, Robert Koch Straße 40, 37075, Goettingen, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone and Bones / cytology
Bone and Bones / embryology
Bone and Bones / pathology
Calcium-Binding Proteins
Cell Adhesion Molecules
Cells, Cultured
Chondrocytes / cytology
Chondrocytes / metabolism
Chondrogenesis / physiology
Collagen Type I / metabolism
Core Binding Factor Alpha 1 Subunit / biosynthesis
Core Binding Factor Alpha 1 Subunit / genetics
Core Binding Factor Alpha 1 Subunit / metabolism*
Discoidin Domain Receptor 1
Disease Models, Animal*
Extracellular Matrix
Membrane Glycoproteins / metabolism
Mice*
Mice, Knockout
Osteoarthritis / genetics*
Osteoarthritis / pathology
Proteoglycans / deficiency
RNA Interference
RNA, Small Interfering
Receptor Protein-Tyrosine Kinases / genetics*
Receptors, Collagen / metabolism
Signal Transduction
Temporomandibular Joint / physiopathology*
Temporomandibular Joint Disorders / genetics*

Substances

Calcium-Binding Proteins
Cell Adhesion Molecules
Collagen Type I
Core Binding Factor Alpha 1 Subunit
Membrane Glycoproteins
Nid2 protein, mouse
Proteoglycans
RNA, Small Interfering
Receptors, Collagen
Runx2 protein, mouse
Ddr1 protein, mouse
Discoidin Domain Receptor 1
Receptor Protein-Tyrosine Kinases