Osteopontin (OPN) is a phosphorylated acidic glycoprotein that has been implicated in a number of physiological and pathological events, including maintenance or reconfiguration of tissue integrity during inflammatory processes. As such, it is required for stress-induced bone remodeling and certain types of cell-mediated immunity. It also acts in dystrophic calcification, coronary restenosis, and tumor cell metastasis. An RGD-containing protein, OPN exists both as an immobilized ECM molecule in mineralized tissues and as a cytokine in body fluids; it is not a significant part of typical nonmineralized ECM.OPN can engage a number of receptors, including the integrins α v (β 1 , β 3 , or β 5 ) and (α 4 , α 5 , α 8 , or α 9 )β 1 , and it may also be a ligand for certain variant forms of CD44, specifically v6 and/or v7, but possibly only in conjunction with a β 1 integrin (1). These receptors directly or indirectly activate cellular signaling pathways, allowing OPN to mediate cell-matrix, and possibly cell-cell, interactions. Several studies have demonstrated that OPN delivers a prosurvival, antiapoptotic signal to the cell. Here, we argue that OPN influences cellular functions in a unique manner, by mimicking key aspects of an ECM signal outside the confines of the ECM. We will explore this idea by reviewing recent data concerning OPN signaling and the consequences of OPN deficiency in several settings, notably inflammatory processes involving immune cells and bone cells. Figure 1 illustrates some of the features of the OPN molecule. The presence of a conserved thrombin cleavage site suggests that certain physiological processes employing OPN depend upon its cleavage by thrombin. Some of these adhesive interactions involve the RGD sequence, which is found in various ECM proteins and binds directly to many integrins. Both RGD-dependent and RGD-independent OPN-receptor interactions are modulated by thrombin cleavage of OPN. For instance, thrombin-cleaved OPN, but not intact OPN, can support RGD-dependent migration of melanoma cells (2). Likewise, K562 erythroleukemia cells bind via activated α 5 β 1 to the RGD sequence in thrombin-cleaved OPN. A non-RGD-dependent interaction with α 9 β 1 offers yet another example: only after cleavage by thrombin can human OPN interact with α 9 β 1 via the sequence SVVYGLR, which is located between the RGD sequence and the thrombin cleavage site (3). This binding motif is also responsible for the RGD-independent binding of the J6 T-cell line to activated α 4 β 1 , but in the latter case, cleavage by thrombin is not required for binding of OPN by activated integrin (4). Adhesion of B lymphocytes via α v β 3 also occurs via a cryptic binding site masked in intact OPN, and TPA-activated B lymphocytes attach more effectively to thrombincleaved OPN than to full-length OPN (5). In contrast, Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival OPN-integrin interactions: consequences of cleavage by thrombin

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.

Objective: To examine the effects of three different parameters-pH value, type of archwire, and length of immersion-on release of metal ions from orthodontic appliances. Materials and Methods: Simulated fixed orthodontic appliances that corresponded to one-half of the maxillary arch were immersed in artificial saliva of different pH values (6.75 Ϯ 0.15 and 3.5 Ϯ 0.15) during a 28-day period. Three types of archwires were used: stainless steel (SS), nickeltitanium (NiTi), and thermo NiTi. The quantity of metal ions was determined with the use of a high-resolution mass spectrophotometer (HR-ICP/MS). Results: The release of six different metal ions was observed: titanium (Ti), chromium (Cr), nickel (Ni), iron (Fe), copper (Cu), and zinc (Zn). Repeated measures statistical analysis of variance (ANOVA) was used. Results showed that (1) the appliances released measurable quantities of all ions examined; (2) the change in pH had a very strong effect (up to 100-fold) on the release of ions; and (3) the release of ions was dependent on wire composition, but it was not proportional to the content of metal in the wire. The largest number of ions was released during the first week of appliance immersion. Conclusion: Levels of released ions are sufficient to cause delayed allergic reactions. This must be taken into account when type of archwire is selected, especially in patients with hypersensitivity or compromised oral hygiene. (Angle Orthod. 2009;79:102-110.)

Keywords -Accelerated orthodontic tooth movement; Effect of vibrations on tooth movement; Effect of vibrations on bone; Cyclic loading and tooth movement; AcceleDent and tooth movement.

Abstract. Type I collagen is expressed in a variety of connective tissue cells and its transcriptional regulation is highly complex because of the influence of numerous developmental, environmental, and hormonal factors. To investigate the molecular basis for one aspect of this complex regulation, the expression of al(I) collagen (COLIA1) gene in osseous tissues, we fused a 3.6-kb DNA fragment between bases -3,521 and +115 of the rat COLIA1 promoter, and three deletion mutants, to the chloramphenicol acetyltransferase (CAT) marker gene. The expression of these CoICAT transgenes was measured in stably transfected osteoblastic cell lines ROS 17/2.8, Py-la, and MC3T3-El and three fibroblastic lines NIH-3T3, Rat-1, and EL2. Deletion of the distal 1 .2-kb fragment of the full-length CoICAT 3.6 construct reduced the promoter activity 7-to 30-fold in the osteoblastic cell lines, twofold in EL2 and had no effect in NIH-3T3 and Rat-1 cells . To begin to assess the function of COLIAI upstream regulatory elements in intact animals, we established transgenic mouse lines and T YPE I collagen is the predominant component of the extracellular matrix and is synthesized by a variety of connective tissue cells . The protein is encoded by two genes, al(I) (COL1A1)' and a2(I) collagen (COLIA2), which are expressed and regulated in a coordinated fashion . Although the regulation oftype I collagen genes is not as dramatic as other highly inducible genes, the control of their expression is extremely complex . Both are single copy nonhousekeeping genes which are active in distinctly different connective tissue cells (Ramirez and Di Liberto, 1990) including : interstitial cells that produce skin, tendon, and the framework of all organs and connective tissues of the body; smooth muscle cells of blood vessels and other viscera ; cartilage cells, in which a different RNA start site is utilized examined the activity of the CoICAT3.6 construct in various tissues of newborn animals . The expression of this construct followed the expected distribution between the high and low collagen-producing tissues : high levels of CAT activity, in calvarial bone, tooth, and tendon, a low level in skin, and no detectable activity in liver and brain . Furthermore, CAT activity in calvarial bone was three-to fourfold higher than that in the adjacent periosteal layer. IJ*munostaining for CAT protein in calvaria and developing tooth germ of CoICAT3 .6 mice also confirmed the preferred expression of the transgene in differentiated osteoblasts and odontoblasts compared to fibroblast-like cells of periosteum and dental papilla . This study suggests that the 3.6-kb DNA fragment confers the strong expression of COLIAI gene in high collagen producing tissues of intact animals and that the 5' flanking promoter sequence between -3,521 and -2,295 by contains one or more stimulatory elements which are preferentially active in osteoblastic cells. (Bennett and Adams, 1990) ; activated fibroblastic cells that are involved in tissue repair and fibrosis ; and osteoblasts and...