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Modulation of osteoblast functions by T lymphocytes is important in inflammation‐associated mineralized tissue diseases. The study aimed to determine whether direct interaction between these two cell types affects osteoblast functions and mineralization. The results showed that direct contact between the two cell types was evident by scanning electron microscopy and transmission electron microscopy. Under osteogenic induction, higher hydroxyapatite precipitation was observed in cocultures with direct contact with T lymphocytes compared with that by osteoblasts cultured alone. Cocultures without direct cell contact caused a decrease in mineralization. Direct cell contact also upregulated intercellular adhesion molecule (ICAM)‐1 and simultaneously downregulated transforming growth factor (TGF)‐β1 in osteoblasts. However, the downregulation of TGF‐β1 was reversed by ICAM‐1 blocking. Exogenously added TGF‐β1 in cocultures with direct cell contact suppressed mineralization. In conclusion, studies are consistent with ICAM‐1‐mediated direct contact between osteoblasts and T lymphocytes increasing mineralization via downregulation of TGF‐β1 in osteoblasts in vitro. This suggests a possible unexpected, but crucial, role of T lymphocytes in enhancing matrix mineralization during the repair process in vivo. The study identifies ICAM‐1/TGF‐β1 as possible novel therapeutic targets for the treatment and prevention of inflammation‐associated mineralized tissue diseases. [ABSTRACT FROM AUTHOR]

Single intact myofibers are transplanted into radiation-ablated muscles to demonstrate that satellite cells are self-sufficient as a source of regeneration. The transplanted satellite cells vigorously self-renew expanding in number and repopulating the host muscle with new satellite cells.

This study has investigated novel bone adhesives consisting of fluid photo-polymerizable poly(lactide- co-propylene glycol- co-lactide)dimethacrylate (PGLA-DMA) mixed with systematically varying fillers of β-tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM), for the delivery of an antibacterial drug chlorhexidine (CHX). All formulations were found to polymerize fully within 200 s after exposure to blue light. In addition, water sorption by the polymerized materials catalyzed varying filler conversion to dicalcium phosphate (DCP) (i.e. brushite and monetite). With greater DCP levels, faster degradation was observed. Moreover, increase in total filler content enhanced CHX release, associated with higher antibacterial activity. These findings thus suggest that such rapid-setting and degradable adhesives with controllable drug delivery property could have potential clinical value as bone adhesives with antibacterial activity. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMP) stimulate osteoblast differentiation by signal transduction via three BMP receptors (BMPR-IA, -IB, and -II). Several growth factors, including transforming growth factor-β1 (TGF-β1), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-AB (PDGF-AB), have also been shown to play an important part in osteogenesis. The mechanism underlying these activities is unclear, but these growth factors could modulate the BMP/BMPR pathway by up-regulating BMPR expression, thereby enhancing the osteogenic responses of bone cells to the BMP. In this study we have therefore examined the effects of TGF-β1, FGF-2, and PDGF-AB on BMPR expression and BMP-2-mediated osteoblast functions in primary human bone cells. The results showed that although the ligand BMP-2 and growth factors had little effect on BMPR-IA and -II transcript expression, they significantly up-regulated BMPR-IB mRNA specifically. However, only the growth factors, but not the ligand BMP-2, increased the surface expression of the BMPR-IB antigen, which was found to be due to a differential effect of BMP-2 and the growth factors on the Smurf1/Smad6-induced breakdown process. Pre-incubation of the cells with the growth factors significantly augmented BMP-2-induced Smad1/5/8 phosphorylation, and Dlx5 expression ALP activity, compared with that of cells treated with BMP-2 alone. When cells were transfected with siRNA targeting BMPR-IB, the growth factors neither up-regulated BMPR-IB transcript expression nor enhanced BMP-2-induced Smad1/5/8 phosphorylation, Dlx5 expression and ALP activity. The results indicate that increased BMPR-IB by TGF-β1, FGF-2, and PDGF-AB significantly enhances BMP-2-induced osteogenic functions in vitro, suggesting that they might positively modulate bone formation by up-regulating BMPR-IB in vivo. J. Cell. Physiol. 209: 912–922, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Inflammation of periodontal tissues during post operative wound healing is mediated by cell surface adhesion molecules. Soluble forms of these antigens have also been identified and shown to be important in immunoregulatory processes, but have previously not been investigated during periodontal repair and regeneration. The present study has examined the presence and possible changes in soluble intercellular adhesion molecule-1 (sICAM-1; CD54) and lymphocyte function-associated antigen-3 (sLFA-3; CD58) in gingival crevical fluid (GCF) following periodontal surgery. Methods: GCF samples were collected from four groups: 1) a guided tissue regeneration (GTR) test; 2) a GTR control, at least one complete tooth unit away from the periodontal defect; 3) a conventional flap (CF) surgery; and 4) a crown lengthening (CL). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of sICAM-1 and sLFA-3 in the GCF samples. Results: A marked increase in GCF volumes was found in all sites after surgery, although a persistent increase was associated only with the period of membrane retention at the GTR test sites. In addition, sICAM-1 and sLFA-3 were found in the GCF of healthy as well as diseased sites prior to treatment and the total amounts of both increased transiently following surgical intervention, especially sLFA-3, However, the concentrations of these GCF components, particularly sICAM-1, tended to decrease. Conclusions: The temporal decrease in the concentration of sICAM-1 and sLFA-3 in GCF may serve to enhance inflammatory reactions at surgically-treated periodontal sites, thereby limiting repair and regeneration in the periodontium. These soluble adhesion molecules may thereby be of potential therapeutic value and might also be useful markers for monitoring periodontal wound healing. [ABSTRACT FROM AUTHOR]

Background: Drug-induced gingival overgrowth (GO) is a frequent and adverse side-effect associated principally with the administration of the immunosuppressive drug cyclosporin A (CsA) and also certain anti-epileptic and anti-hypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and the accumulation of excessive amounts of connective tissue. Although the mechanism by which the drugs cause GO is not yet understood, keratinocyte growth factor (KQF), which is a potent epithelial cell mitogen, has been implicated in other hyperplastic conditions, including mammary and prostatic hyperplasia, and could also be involved in the molecular pathology of GO. Methods: Immunohistochemistry was used to examine the expression of KGF in normal gingiva (NG) and CO tissue sections. The relative level of KGF mRNA in GO tissue and cells was compared with that of NG tissue and fibroblast cells using the semi-quantitative reverse transcribed-polymerase chain reaction (RT-PCR) and DNA sequencing was carried out to confirm the identity of the PCR product. Results: KGF antigen and mRNA were readily detected in the GO tissue immunohistochemically and by RT-PCR, respectively, but were not expressed in the NG tissue. Moreover, KGF transcripts were found to be approximately 2 times higher in the GO than in the NG fibroblasts in vitro, although the difference was not statistically significant. Conclusions: This study has shown, for the first time, that the level of KGF is elevated in GO and suggests that KGF may have an important role in the enhanced epithelial proliferation associated with GO. [ABSTRACT FROM AUTHOR]

Murine and human cells (mainly lymphocytes) were methylated with either N-[C]methyl-N-nitrosourea (MNU) or di-[C] methyl sulphate (DMS) and the extents of methylation of DNA at O-6 and N-7 of guanine and N-3 of adenine were determined. The cytotoxic action of MNU was also compared with that of DMS, as assessed by their effects on cell division following stimulation of these lymphocytes in culture by concanavalin A (Con A). The overall extent of methylation of the DNA of human cells was about 70% of that of murine cells after exposure to MNU and DMS. Mouse cells, responding to Con A in culture, were found to be much more sensitive to both agents than could be accounted for by these differences in overall extent of methylation of the DNA. Significant differences were found between cells in their ability to rapidly remove O-methylguanine from DNA. Normal human lymphocytes were always proficient, but some human lymphoid lines were deficient in this respect, while all the murine cells tested were deficient, as found for mouse lymphoid tissues. No correlation has yet been found between the susceptibility of various mouse strains to the carcinogenic action of MNU and their ability to remove methylated bases from DNA. The cytotoxicity studies, showing that normal human lymphocytes were relatively more resistant than murine cells to methylation by both MNU and DMS, suggested that the ability to remove O-methylguanine (which is produced in a very low proportion by DMS) was not of prime importance in conferring resistance in this type of assay. [ABSTRACT FROM PUBLISHER]

The oral form of the inflammatory disease lichen planus occurs spontaneously due to unknown aetiological factors. However, it has recently been observed to occur with increased frequency in patients infected with the hepatitis C virus. Because of the prominent role of adhesion molecules in immune cell interactions, we have compared the expression of these antigens in the hepatitis C virus-associated and idiopathic forms of the disease. The results show similar patterns of expression of very late activation antigen-4, lymphocyte function-associated antigen-3 and intercellular adhesion molecule-1, but relatively elevated levels of these antigens in oral lichen planus patients with no hepatitis C virus infection. In addition to differences in Langerhans cell distribution, serum levels of "soluble" intercellular adhesion molecule-1 as well as immunoglobulin G were significantly increased in the hepatitis C virus-associated group. These findings show that there are some differences in the lesional and systemic immune reactivities of the two types of oral lichen planus which may be related to possibly distinct pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Fibronectin is a major component of the extracellular matrix and is considered to have an important role in chronic inflammatory periodontal disease. The fibronectin gene product has been shown to be subject to alternative splicing in 3 regions, each generating different mRNA transcripts associated specifically with normal adult tissue, embryogenesis, tissue regeneration, and wound healing. In the present study, using the reverse-transcribed polymerase chain reaction to examine splicing profiles of the primary transcript, we found that healthy periodontal tissue expressed all alternatively spliced embryonic isoforms, indicative of the extensive and ongoing rebuilding processes which occur in these tissues. In marked contrast, only the exon-skipped transcripts were generated in tissue from chronic inflammatory periodontal disease patients. The loss of the high molecular weight isoforms in lesional tissues may be due to the excess production of inflammatory mediators in this disease, since we observed that high concentrations of the cytokine IL-1β caused down-regulation of these transcripts in normal periodontal cells in tissue culture. Moreover, we also demonstrated that growth factors likely to be involved in periodontal regeneration and repair, such as PDGF, IGF- 1 and TGF-β, elicited pronounced upregulation of the embryonic isoforms of fibronectin in these cells. Although the functional activities of the antigens corresponding to the alternatively spliced variants of fibronectin are not yet known, our finding that they are selectively expressed suggests that they have highly specific roles in both periodontal breakdown and repair. [ABSTRACT FROM AUTHOR]