Biological roles of Dmp-1 during development of mandible and temporomandibular joint

Objectives: Dentin matrix protein-1 (Dmp-1) is closely associated with dentin formation, and also highly expressed in mineralized tissues. However, the role of Dmp-1 in skeletal tissues remains unclear. Methods: To clarify the role of Dmp-1 during development of mandible and temporomandibular joint (TMJ), in situ hybridization was performed to examine the spatial and temporal expression patterns of Dmp-1 during development in mouse embryos from 12.5 dpc to 8-week postnatal. And changes in the mandible and TMJ of Dmp-1 knockout mice were also evaluated with HE staining, TEM and radiographic examination. Results: In situ hybridization study demonstrated that Dmp-1 first appeared in hypertrophic cartilage cells, followed by osteoblasts, and later was strongly expressed in osteocytes. Dmp-1 knockout mice presented delayed or irregular ossification in the mandible or TMJ starting from 2-3 weeks after birth. The normally uniform growth plates were replaced by thickened, disordered and nodular shaped growth plates with an apparent increase in the proportion of hypertrophic cells. The growth plate and articular cartilage layer in Dmp-1 knockout mice were irregular with no well-formed trabecular bone. The overall sizes of the skull and jaws of Dmp-1 knockout mice were smaller than that of wild type mice and the bone density is obviously decreased with many bony cysts and erosions. Conclusions: Our results revealed that Dmp-1 is a marker gene for chondrocytes and osteoblasts during early skeletogenesis and for osteocytes in the mature skeleton, and suggested that Dmp-1 may be an essential molecule for formation and differentiation of the growth plate and trabecular bone remodelling.