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Dentin Matrix Protein 1 (DMP1): New and Important Roles for Biomineralization and Phosphate Homeostasis
C. Qin,
R. D’Souza and
J.Q. Feng*
Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA
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Figure 1. DMP1 is highly expressed in mineralized tissues. (a) A whole-mount X-gal stain of an E15.5 Dmp1-lacZ knock-in embryo (left panel) and the insert (right panel), with an enlargement of the area outlined in the left panel re-stained with x-gal, show high lacZ expression in osteoblasts. Note that a lacZ reporter gene was used to replace exon 6 of the Dmp1 gene. The expression of lacZ, as demonstrated by X-gal staining, reflects endogenous Dmp1 expression. (b) A whole-mount X-gal stain of a skeleton from an 8-day-old Dmp1-lacZ knock-in pup with lacZ expressed in osteocytes (the enlarged insert). (c) DMP1 immunostain of bone matrix surrounding osteocytes (signal in brown). Both assays suggest that DMP1 is mainly expressed in the osteoblasts during embryonic development, and that this matrix protein is predominantly expressed in the osteocytes during postnatal development. (d) Summary of Dmp1-lacZ expression profiles in all hard tissues. Part of this Fig. is adapted from Feng et al.(2003).
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Figure 2. DMP1 controls osteogenesis and dentinogenesis. (a) Resin-embedded alveolar bone (3-month-old) was acid-etched to remove mineral, leaving behind the plastic for visualization of the osteocyte lacuno-canalicular system by scanning electron microscopy (SEM). (b) SEM images of a fractured 1st molar (upper panel, 3-month-old), and resin-cast dentin tubules (lower panel, dentin tubules filled with resin), showing the normal structure of dentin. (c) The current working hypothesis: DMP1 is required for both osteogenesis and odontogenesis by controlling cell differentiation and maturation, as well as mineralization. The deletion of DMP1 results in defects in both processes. Part of the Figure is adapted from Ye et al.(2004) and Feng et al.(2006).
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Figure 3. Mice lacking DMP1 display defects in mineralization. (a) TEM images of 3-month-old tibias showing that the mineral matrix (black) surrounding the control osteocyte is smooth (left panel), and that spherical structures of calculo-spherulites were present in Dmp1-KO mice, with markedly reduced propagation into the surrounding osteoid (right panel, arrow). (b) Images of back-scattered SEMs of tibias (samples were treated with osmium to preserve cell morphology) show poor mineral matrix (white) surrounding KO osteocytes (right). *(c) Confocal microscopy images of fluorochrome labeling, counterstained with DAPI for visualization of osteocyte nuclei (blue). The Dmp1-KO osteocytes are buried in diffuse fluorochrome label, suggesting a defect in the process of mineral propagation (right panel). (d) H&E-stained sections of molars show an extended predentin (red layer in newly formed dentin matrix) and reduced dentin in Dmp1 null mice (KO), compared with the control (Cont) mice. (e) Back-scattered SEM images reveal a dramatic decrease in mineral (white color), plus a striking change in dentin matrix structure (right panel) compared with the control mice. The data are adapted from Ye et al.(2004) and Feng et al.(2006).
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Figure 4. DMP1 controls Pi homeostasis through FGF23. (a) In situ hybridization shows a sharp increase in FGF23 mRNA (red) from 10-day-old Dmp1-KO osteocytes obtained from jaws (upper panel, control; lower panel, KO). The data are adapted from Feng et al.(2006). (b) Summary of defects of Pi homeostasis in Dmp1-KO mice. Note that FGF23 is mainly released from normal osteoblasts, which targets kidneys for inhibition of Pi re-absorption. In pathological conditions such as mutations of DMP1 or deletion of Dmp1, overproduction of FGF23 in bone leads to hypophosphatemia rickets, including defects in the epiphyses and growth plate.
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Journal of Dental Research, Vol. 86, No. 12,
1134-1141 (2007)
DOI: 10.1177/154405910708601202
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