Dentin matrix protein 1 (DMP-1) is a key molecule in controlling osteocyte formation and phosphate homeostasis. Based on observations that full-length DMP-1 is not found in bone, but only cleaved fragments of 37 and 57 kDa are present, and in view of the finding that mutations in the 57-kDa fragment result in disease, we hypothesized that the 57-kDa C-terminal fragment is the functional domain of DMP-1. To test this hypothesis, a 3.6-kb type I collagen promoter was used to express this 57-kDa C-terminal fragment for comparison with full-length DMP-1 in Dmp1 null osteoblasts/osteocytes. Not only did expression of the full-length DMP-1 in bone cells fully rescue the skeletal abnormalities of Dmp1 null mice, but the 57-kDa fragment also had similar results. This included rescue of growth plate defects, osteomalacia, abnormal osteocyte maturation, and the abnormal osteocyte lacunocanalicular system. In addition, the abnormal fibroblast growth factor 23 (FGF-23) expression in osteocytes, elevated circulating FGF-23 levels, and hypophosphatemia were rescued. These results show that the 57-kDa C-terminal fragment is the functional domain of DMP-1 that controls osteocyte maturation and phosphate metabolism. © 2011 American Society for Bone and Mineral Research.

To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal-and spatial-expression pattern of OSX and the formation of cellular cementum. We then generated 3.6 Col 1-OSX transgenic mice, which displayed accelerated cementum formation vs. WT controls. Importantly, the conditional deletion of OSX in the mesenchymal cells with two different Cre systems (the 2.3 kb Col 1 and an inducible CAG-CreER) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the OSX gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered SEM and resin-cast SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support 1) the mesenchymal origin of cellular cementum (from PDL progenitor cells); 2) the vital role of OSX in controlling the formation of cellular cementum; and 3) the limited remodeling of cellular cementum in adult mice.

This paper develops a Monte Carlo simulation (MCS)-based reliability analysis approach for slope stability problems and utilizes an advanced MCS method called “subset simulation” for improving efficiency and resolution of the MCS at relatively small probability levels. Reliability analysis is operationally decoupled from deterministic slope stability analysis and implemented using a commonly available spreadsheet software, Microsoft Excel. The reliability analysis spreadsheet package is validated through comparison with other reliability analysis methods and commercial software. The spreadsheet package is then used to explore the effect of spatial variability of the soil properties and critical slip surface. It is found that, when spatial variability of soil properties is ignored by assuming perfect correlation, the variance of the factor of safety (FS) is overestimated, which may result in either over (conservative) or under (unconservative) estimation of the probability of failure (Pf = P(FS < 1)). When the spatial variability of soil properties is considered, the critical slip surface varies spatially and such spatial variability should be properly accounted for. Otherwise, the probability of failure can be significantly underestimated and unconservative.

Baicalin protects against tissue damage in ligature-induced periodontitis in rats, which might be mediated, in part, by its inhibitory effect on the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These activities could support the continued investigation of baicalin as a potential therapeutic agent in periodontal disease.