Msx2 and Dlx2 expressions and functions during alveolar bone growth

Objectives: Defect in tooth development affect alveolar bone and reversely as observed in osteopetrosis. Homeobox genes from Msx and Dlx families have been implicated in tooth development from early to late stages. During tooth histogenesis, Msx2 and Dlx2 expression patterns have been established suggesting that these genes are implicated in tooth volumetric growth through the control of enamel synthesis and root elongation. In contrast, Msx2 and Dlx2 implication in the associated alveolar bone growth has been poorly analyzed. The aim of the present study was so to determine these two genes expressions in the alveolar bone cells and to analyze Msx2 gene null mutation impact onto alveolar bone.

Methods: Dlx2/LacZ and Msx2/LacZ transgenic mice were used to establish expression patterns in alveolar bone cells. Msx2 null mutant mice (KO) alveolar bone phenotype was analyzed by classical histology. Alveolar bone cells markers (for instance osteocalcin of osteoblasts and TRAP for osteoclasts) and signaling molecules toward bone cells (RANKL for example) were comparatively analyzed between wild type and Msx2 KO mice using quantitative RT-PCR and immuno-histochemistry.

Results: Analysis of transgenic mice evidence that both Msx2 and Dlx2 are expressed only by some osteoclasts with highest expression levels found in active sites of bone modeling associated with tooth volumetric growth. Histology shows that Msx2 KO mice displayed a wide spectrum of alterations in tooth and alveolar bone (osteopetrosis). Expression of bone markers appears to be reduced and the RANKL-RANK pathway seems to be the most affected one.

Conclusion: This study establishes that in addition to their expression in dental cells during tooth histogenesis, Msx2 and Dlx2 homeobox genes are also expressed by alveolar bone osteoclasts. The null mutation of Msx2 induces severe phenotypes of tooth and alveolar bone that could be partly the consequence of signaling pathways alterations.