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Matrix Gla Protein Inhibition of Tooth Mineralization
N.R. Kaipatur1,
M. Murshed1,2 and
M.D. McKee1,3,*
1 Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, Canada H3A 2B2;
2 Department of Medicine, McGill University, Montreal, QC, Canada; and
3 Department of Anatomy and Cell Biology, McGill University, QC, Montreal
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Figure 1. Transgene promoter expression, MGP localization, and radiography and micro-computed tomography (microCT) of transgenic and wild-type mice. (A) X-gal staining showing the activity of the 2.3-kb Col1a1 promoter driving bacterial β-galactosidase (lacZ) expression in the mandible (oval outline) of a four-day-old Col1a1-LacZ mouse. (B–D) Immunohistochemistry showing MGP localization after transgene expression in three-week-old Col1a1-Mgp incisor root analogue dentin (asterisk, B) and surrounding alveolar bone (asterisk, C); no MGP is found in wild-type dentin (D) or alveolar bone. (E,F) Radiographs (insets) of three-week-old hemimandibles from wild-type and Col1a1-Mgp mice demonstrate overall increased radiolucency (hypomineralization) in the tooth root area and in the mandibular bone of the transgenic mice. MicroCT reconstructions along the mid-sagittal plane of the incisor in wild-type and transgenic hemimandibles confirm the complete lack of mineralized molar roots (white arrow) and incisor root analogue (black arrow), and show an increase in bone porosity in the alveolar bone, from decreased mineralization in the Col1a1-Mgp samples. (G–J) Reconstructed and single-slice cross-sectional microCT profiles at the level of the first molar similarly demonstrate a lack of mineralization of the tooth roots (molar, white arrows; incisor, black arrows) and surrounding alveolar bone in the Col1a1-Mgp mice. M1, first molar; M2, second molar; R, roots of molars; RA, root analogue of incisor; CA, crown analogue of incisor; I, incisor. Magnification bars equal 50 µm. (This Fig. is available in color online.)
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Figure 2. Total (A) and relative (B) mineralized tissue volumes obtained by quantitative microCT from hemimandibles of wild-type and Col1a1-Mgp mice ranging in age from 1–12 wks. Significant decreases in Col1a1-Mgp vs. wild-type mineralized tissue volumes are observed at most of the ages examined. MTV, mineralized tissue volume; TV, total tissue volume. N = 3 for each genotype. Data are shown as the mean ± SE. *P < 0.05, **P < 0.01, ***P < 0.001.
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Figure 3. Light micrographs of von Kossa-stained (black areas, mineral) sections from undecalcified hemimandibles, and histomorphometry, of wild-type and Col1a1-Mgp mice. Wild-type incisors and bone at 1 wk (A) and 3 wks (B) of age, and wild-type first molar at 3 wks of age (C), showing well-mineralized tooth and bone extracellular matrices. Col1a1-Mgp incisors and bone at 1 wk (D) and 3 wks (E) of age, and Col1a1-Mgp first molar at 3 wks of age (F), showing well-developed tooth and bone extracellular matrices, but with an absence of, or substantial decreases in, mineralization. Molar root dentin, incisor root analogue dentin, and alveolar bone were all particularly hypomineralized, whereas molar crown dentin and incisor crown analogue dentin typically were less affected and showed breakthrough dentin mineralization, which interfaced with mineralized enamel. Osteodentin was also sometimes present in the pulp chambers of the Col1a1-Mgp molars. Histomorphometry of incisor root analogue (G) and crown analogue (H) dentin from wild-type and Col1a1-Mgp mice of different ages showing significantly higher amounts of unmineralized dentin in the transgenic mice. (I) Similarly, unmineralized osteoid in Col1a1-Mgp was substantially increased compared with that in wild-type littermates. En, enamel; Den, dentin; Os-Den, osteodentin. Magnification bars equal 100 µm. (G–I) N = 3 for each genotype. Data are shown as the mean ± SE. *P < 0.05, **P < 0.01, ***P < 0.001. (This Fig. is available in color online.)
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Figure 4. Light micrographs after von Kossa staining for mineral (black areas), and electron micrographs, of undecalcified three-week-old Col1a1-Mgp mandibular teeth and alveolar bone. Light micrographs in the left panels show regions selected for electron microscopy (box frame) as presented in the right panels. (A,B) Incisor dentin extracellular matrix and associated periodontal tissues show typical histology in terms of cellular and matrix distribution and organization, although acellular cementum was lacking at the root surface (asterisks). However, although there was a generalized absence of mineralization in the dentin, small mineralization foci were frequently observed by TEM throughout the matrix (inset). (C,D) In molars, as for dentin, the extracellular matrix of cellular cementum was generally unmineralized, and showed similar small mineralization foci dispersed throughout the matrix (inset). Osteodentin, which, like alveolar bone, showed variable levels of mineralization (but in this sample is not mineralized), was occasionally observed within the pulp. (E,F) Alveolar bone, while having profound osteoidosis, also had many areas of extensive, but incomplete, mineralization. Shown here are large unmineralized areas, and thickened osteoid seams. At the mineralization front adjacent to the thickened osteoid, an unusual band of mineral texture was observed (arrows) adjacent to the mineralized matrix proper. Again, small mineralization foci were distributed throughout the otherwise unmineralized osteoid (inset). Den, dentin; PDL, periodontal ligament; Od, odontoblast; Os-Den, osteodentin; C-Cem, cellular cementum; Ob, osteoblast. Magnification bars equal 50 µm (A,C,E), 5 µm (B,D,F), and 50 nm (insets).
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Journal of Dental Research, Vol. 87, No. 9,
839-844 (2008)
DOI: 10.1177/154405910808700907
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