Logo Deutscher Zahnärztetag Dr. Boris Schminke (Göttingen)

Dr. Boris Schminke (Göttingen) et al.

The discoidin domain receptor 1 deficient mice for the investigation of osteoarthritis in the temporomandibular joint

Temporomandibular disorders are structural, functional, biochemical and psychological dysregulations of muscle or temporomandibular joint (TMJ) functions. Most patients suffer from severe pain in the muscles of mastication and the TMJ. Temporomandibular disorders show numerous pathological findings like joint clicking, displacement or perforation of the articular disc and inflammatory or degenerative changes of the TMJ, such as osteoarthritis (OA).

OA is a degenerative disease, in which the balance between cartilage degradation and matrix synthesis is disturbed, resulting in the complete loss of joint function. Especially in the TMJ, even a flattening of the condyle occurs. Recently, we demonstrated that repair tissue from human articular knee cartilage during the late stages of osteoarthritis harbors a unique progenitor cell population, termed chondrogenic progenitor cells (CPCs). These cells show stem cell characteristics such as clonogenicity, multipotency, and a migratory activity. CPCs are regulated via the osteogenic transcription factor runx2 and the chondrogenic transcription factor sox9.

It is still unknown whether progenitor cells also play a role in regeneration attempts of the TMJ. Here we introduce the discoidin domain receptor 1 (DDR1) deficient mice as a new model for OA in the TMJ. DDR1 knockout mice exhibit the typical histological characteristics of OA, for example, cluster formation and surface fissures. Toluidin blue staining, indicating the proteoglycan content, is decreased. Furthermore, the amount of collagen type I is increased, while collagen type II is decreased. Electron microscopy reveals an altered collagen fiber network. The real time PCR data and FACS analysis confirm the osteoarthritic character of the DDR1 deficient mice, for example, high amounts of runx2 and collagen type I as well as low levels of sox9 and aggrecan.

We conclude that, DDR1, an extracellular matrix sensing receptor tyrosine kinase, which binds to several collagens, is involved in the pathogenesis of OA in TMJ. Moreover, preliminary results indicate, that a subpopulation of hTERT immortalized chondrocytes from the TMJ of DDR1 knockout mice represent chondrogenic progenitor cells.
Copyright © 2011 Quintessenz Verlags-GmbH, Berlin