Abstract
Glucose-regulated protein 78 (GRP-78) is one of the many endoplasmic reticulum chaperone proteins that have been shown to possess multifunctional roles. We have previously demonstrated that GRP-78 functions as a receptor for dentin matrix protein 1 (DMP1) and is required for DMP1-mediated calcium release; that it is a secreted protein and can bind to type I collagen and DMP1 extracellularly and aid in the nucleation of calcium phosphate. We provide evidence in this study that tyrosine phosphorylation is required for DMP1/GRP-78-mediated calcium release in mesenchymal cells. We further demonstrate that GRP-78 is localized in the nucleus of mesenchymal cells and that the cell surface GRP-78 is not associated with the G-protein Gαq in mesenchymal cells. Results from this study show that during development of mineralized tissues, increased expression of GRP-78 can be observed in condensing cartilage and mesenchymal cells of the alveolar bone, endochondral bone and dental pulp. Additionally, we show that GRP-78 is present in the mineralizing matrices of teeth, bone and in the extracellular matrix of differentiating human marrow stromal cells and dental pulp stem cells. Collectively, our observations provide a new perspective on GRP-78 with respect to mineralized matrix formation.
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This work was supported by grant from National Institutes of Health DE 11657 and the Brodie Endowment Fund.
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418_2012_952_MOESM1_ESM.tif
Supplementary Figure 1: Expression of GRP-78 during postnatal tooth development.(A) Enlarged image of figure 2C showing presence of GRP-78 in the dentin matrix and secretory odontoblasts at day 3. (B) Enlarged image of figure 3B showing the presence of GRP-78 in the mineralizing dentin matrix at day 5. (C, D) Images showing increased expression of GRP-78 in condensing hypertrophic chondrocytes of the alveolar bone at post natal days 3 and 7 respectively. (TIFF 1054 kb)
418_2012_952_MOESM2_ESM.tif
Supplementary Figure 2: Expression of GRP-78 in developing long bone.(A, B) Same images as in figure 4C and 4D overlayed with collagen autofluorescence to show the presence of bone matrix. (TIFF 1585 kb)
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Ravindran, S., Gao, Q., Ramachandran, A. et al. Expression and distribution of grp-78/bip in mineralizing tissues and mesenchymal cells. Histochem Cell Biol 138, 113–125 (2012). https://doi.org/10.1007/s00418-012-0952-1
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DOI: https://doi.org/10.1007/s00418-012-0952-1