Mechanical Loading Stimulates Dentin Matrix Protein 1 (DMP1) Expression in Osteocytes In Vivo

Abstract

Dentin matrix protein 1 (DMP1) was originally postulated to be dentin specific. Further analysis showed that DMP1 is also expressed in mature cartilage and bone. In bone tissue, DMP1 is expressed predominantly in late osteoblasts and osteocytes. DMP1 belongs to the SIBLING (Small Integrin Binding Ligand N-linked Glycoprotein) family of cellular matrix proteins that also includes osteopontin, bone sialoprotein, dentin sialophosphoprotein, and others. In this study, we examined the effect of mechanical loading on expression of DMP1 mRNA and DMP1 protein in alveolar bone in the mouse tooth movement model by in situ hybridization and immunocytochemistry. The expression of DMP1 mRNA was determined quantitatively in mechanically loaded and control sites of dento-alveolar tissue at several time points from 6 h to 7 days after loading. The tooth movement model allows simultaneous evaluation of bone resorption and bone formation sites. Expression of DMP1 mRNA in osteocytes increased 2-fold as early as 6 h after treatment in both the bone formation and bone resorption sites. After 4 days, DMP1 expression in osteocytes increased to a maximum of 3.7-fold in the bone formation sites and 3.5-fold in the resorption sites. Osteoblasts responded in the opposite manner and showed a transient 45% decrease of DMP1 mRNA in bone formation sites and a constant decrease of DMP1 mRNA during the entire course of treatment in the bone resorption sites, with a peak inhibition of 67% at day 2. By immunocytochemistry using a C-terminal region peptide antibody to DMP1, we found that there was a transient decrease in immunoreactivity at 3 days after treatment on both the formation side and the resorption side compared with the matched contralateral control tissue. However by 7 days of loading, there was a dramatic increase in DMP1 protein immunoreactivity on both the formation side and the resorption side. These results represent changes in epitope availability using this antibody or true changes in protein levels.

Evidence for the Proteolytic Processing of Dentin Matrix Protein 1

“…Immunohistochemical studies have demonstrated that signals for PHEX protein are stronger in osteocytes than in osteoblasts and localized predominantly on the plasma membrane (35). Likewise, DMP1 in bone is more highly expressed in osteocytes than in osteoblasts (36,37). This coincidental localization of DMP1 and PHEX protein in osteocytes and osteoblasts strengthens the possibility that PHEX protein may be the proteinase involved in the processing of DMP1.…”

Fibromodulin and Biglycan Modulate Periodontium through TGFβ/BMP Signaling

“…In the present study, expression of DMP1 in incisor PDL was enhanced progressively within the PDL region with age in dKO vs. WT mice. DMP1 is suggested to be a mechanosensor, with increased expression in mechanically loaded osteocytes (Gluhak-Heinrich et al, 2003). It is important to note that rodent incisors are continuously growing.…”

Molecular pathways mediating mechanical signaling in bone

“…As well, unloading causes osteopontin expression in osteocytes (Gross et al, 2005). Dentin matrix protein (DMP1), which is a secreted matrix protein expressed in late osteoblasts and osteocytes, has been shown to increase in osteocytes after tooth movement in the jaw (Gluhak-Heinrich et al, 2003).…”