Abstract
Temporomandibular joint (TMJ) disorders are often associated with development of osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor 2 (DDR2), a collagen receptor preferentially activated by type I and III collagen found in the TMJ and other fibrocartilages, has been associated with TMJ degeneration, but its role in normal joint development has not been previously examined. Using
Ddr2 LacZ
-tagged mice and immunohistochemistry, we found that DDR2 is preferentially expressed and activated in the articular zone of TMJs but not knee joints. To assess the requirement for Ddr2 in TMJ development, studies were undertaken to compare wild-type and
smallie
(
slie
) mice, which contain a spontaneous deletion in
Ddr2
to produce an effective null allele. Analysis of TMJs from newborn
Ddr2
slie/slie
mice revealed a developmental delay in condyle mineralization, as measured by micro–computed tomography and histologic analysis. In marked contrast, knee joints of
Ddr2
slie/slie
mice were normal. Analysis of older
Ddr2
slie/slie
mice (3 and 10 mo) revealed that the early developmental delay led to a dramatic and progressive loss of TMJ articular integrity and osteoarthritis-like changes. Mutant condyles had a rough and flattened bone surface, accompanied by a dramatic loss of bone mineral density. Mankin scores showed significantly greater degenerative changes in the TMJs of 3- and 10-mo-old
Ddr2
slie/slie
mice as compared with wild-type controls. No DDR2-dependent degenerative changes were seen in knees. Analysis of primary cultures of TMJ articular chondrocytes from wild-type and
Ddr2
slie/slie
mice showed defects in chondrocyte maturation and mineralization in the absence of
Ddr2
. These studies demonstrate that DDR2 is necessary for normal TMJ condyle development and homeostasis and that these DDR2 functions are restricted to TMJ fibrocartilage and not seen in the hyaline cartilage of the knee.