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Tuula Salo

Publications and source records attributed to Tuula Salo.

At least 19 recordsLinked to original sources
PubMed2007

Claudins 1, 4, 5, 7 and occludin in ameloblastomas and developing human teeth.

BACKGROUND: To analyze the distribution pattern of claudins 1, 4, 5, 7 and occludin in benign and malignant ameloblastomas and developing human teeth. METHODS: Paraffin-embedded tissue specimens of 25 benign and four malignant ameloblastomas and two developing human teeth were examined immunohistochemically using antibodies against claudins 1, 4, 5, 7 and occludin. RESULTS: In ameloblastomas strongest expression was seen for claudins 1 and 7 while claudin 4 was expressed less frequently. Claudin 5 and occludin were seen only in a minority of cases. There were no evident differences in the expression of claudins or occludin neither between different histologic subtypes of ameloblastomas nor between benign or malignant cases. The strongest expression for claudins was present in the central stellatum reticulum-like cells surrounding the microcysts and in the areas with squamous differentiation of the ameloblastomas. In developing teeth both claudin 1 and 7 stained strongly in the enamel epithelium, ameloblasts, and enamel matrix, but staining for claudin 4 was relatively weak. Claudin 5 was preferentially expressed only in vessels, and occludin staining ranged from negative to weak in ameloblastomas and teeth germs. CONCLUSION: There were no clear differences in the expression levels between benign and malignant ameloblastic tumors. The overexpression of claudins in the areas with microcyst formation may indicate their attempt to maintain the interepithelial cohesion of the cells. The strong immunoreactivity of ameloblasts and newly synthesized enamel matrix for claudins 1 and 7 indicates that they may be involved in cell signaling influencing enamel formation.

Ameloblastoma↗
PubMed2007

Collagen XVIII modulation is altered during progression of oral dysplasia and carcinoma.

BACKGROUND: Collagen XVIII is a ubiquitous basement membrane (BM) component and a precursor of endostatin. METHODS: Using immunohistochemistry and in situ hybridization, we studied the expression and localization of collagen XVIII in different stages of normal oral wound healing, epithelial dysplasia and squamous cell carcinoma (SCC). RESULTS: In mild epithelial dysplasias collagen XVIII appeared as a continuous signal in the BM, whereas in severe epithelial dysplasias and in the invasive areas of oral SCCs collagen XVIII was absent. In situ hybridization showed that collagen XVIII mRNA expression did not decrease in severe dysplasia or oral carcinoma samples when compared with the mild dysplasias. CONCLUSIONS: The results indicate that the absence of collagen XVIII protein in severe oral dysplasias is related to the processing of the protein rather than to changes in mRNA expression.

Angiogenesis Inhibitors↗
PubMed2006

Matrix metalloproteinase-8 (MMP-8) is the major collagenase in human dentin.

OBJECTIVE: Previously an unidentified collagenolytic metalloprotease together with gelatinase (matrix metalloproteinase-2, MMP-2), and enamelysin (MMP-20) have been detected in human dentin. The aim of the study was to characterize dentinal collagenolytic enzymes. Furthermore, we hypothesized that the dentinal MMPs are protected by the mineral phase, and studied the stability of dentinal MMPs. DESIGN: To characterize dentinal collagenolytic enzymes, we used Western blotting with specific antibodies against MMP collagenases (MMP-1, -8, and -13) and cathepsin K. MMP-8 immunofluorometric assay (IFMA) was also used for MMP-8 detection, and functional collagenase activity was examined with type I collagen degradation assay. The stability of dentinal MMPs was examined by autoclaving dentin blocks before protein extraction and subsequent examination of protein levels and the activities of dentin collagenase and gelatinases. RESULTS: MMP-8 (collagenase-2) was detected in dentin both with Western blot and IFMA, and dentinal samples also cleaved the intact type I collagen into characteristic 3/4(alphaA)-cleavage products in vitro. No other collagenases or cathepsin K were detected. In autoclaved samples no MMP-8 was found, but gelatinase activity was observed in protein fractions of mineralized dentin. CONCLUSIONS: MMP-8 represents the major collagenase in human dentin. Unlike MMP-8, dentinal gelatinases can be detected after autoclave treatment of dentin, indicating their high resistance to external sample treatment procedures.

Adult↗
PubMed2006

Human tongue carcinoma growth is inhibited by selective antigelatinolytic peptides.

Matrix metalloproteinases (MMP-2 and MMP-9, or gelatinases) are involved in tongue SCC invasion, metastasis and angiogenesis. We have recently shown that a novel and selective hydrophobic cyclic CTTHWGFTLC (CTT1) peptide is inhibitor for MMP-2 and MMP-9 (Koivunen et al., Nat Biotechnol 1999; 17:768-74). In this study, we demonstrate that both the new hydrophilic derivate GRENYHGCTTHWGFTLC (CTT2) peptide and the CTT1 peptide inhibited specifically the human tongue squamous cell carcinoma (HSC-3) cell-derived gelatinolytic activity and in vitro invasion and migration of these cells (p < or = 0.049). In situ zymography revealed that both peptides also inhibited clearly almost all of the gelatinolytic activity present in the human tongue SCC tissue sections, indicating that MMP-2 and MMP-9 are the major gelatinases detected in the tongue carcinomas. However, CTT2 did not inhibit the type I collagen degradation by human collagenases (MMP-1, MMP-8 and MMP-13). Furthermore, CTT2 reduced the blood vessel density (p < or = 0.043) and clearly improved the survival of the mice bearing human tongue carcinoma xenografts (p < or = 0.012). Overall, we suggest that CTT1 and CTT2 peptides being selective gelatinase inhibitors with significant anti-tumor properties could be useful to diminish the invasion and angiogenesis of human tongue carcinomas characterized by enhanced gelatinolytic activity in tumors.

Carcinoma↗
PubMed2006

Stabilization of the activated alphaMbeta2 integrin by a small molecule inhibits leukocyte migration and recruitment.

Integrins are potential targets for the development of antiinflammatory agents. Here we develop a novel high-throughput assay by allowing a chemical library to compete with phage display peptide binding and identify a novel small-molecule ligand to the leukocyte-specific alpha(M)beta(2) integrin. The identified thioxothiazolidine-containing compound, IMB-10, had an unexpected activity in that it stabilized binding of alpha(M)beta(2) to its endogenous ligands proMMP-9 and fibrinogen. Single amino acid substitutions in the activity-regulating C-terminal helix and the underlying region in the ligand-binding I domain of the integrin suppressed the effect of IMB-10. A computational model indicated that IMB-10 occupies a distinct cavity present only in the activated form of the integrin I domain. IMB-10 inhibited alpha(M)beta(2)-dependent migration in vitro and inflammation-induced neutrophil emigration in vivo. Stabilization of integrin-mediated adhesion by a small molecule is a novel means to inhibit cell migration and may have a utility in treatment of inflammatory diseases involving leukocyte recruitment.

Amino Acid Sequence↗
PubMed2006

Trypsins and their role in carcinoma growth.

There are more than 100 distinct types of cancer, and subtypes can be found within specific organs. Cancer progression is a complex multi-step process. These steps reflect alterations that drive the progressive transformation of normal cells into highly malignant ones. One critical step in tumor growth and invasion is the proteolytic processing of the extracellular matrix environment. The degradation of the extracellular matrix not only enables cell migration, invasion, and metastasis formation, but also affects cell behavior in multiple ways; on one hand by cleaving extracellular matrix bound growth factors and on the other hand by inhibiting angiogenesis into the tumor by liberating cryptic endogenous inhibitors of angiogenesis. Serine proteases and matrix metalloproteases are families of proteolytic enzymes involved in physiological and pathological extracellular matrix and basement membrane processing. In this review, we will focus on the role and activation of trypsinogens, a family of serine proteases, in cancer progression.

Angiogenesis Inhibitors↗
PubMed2006

Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation.

Matrix metalloproteinases (MMPs) form a family of enzymes that mediate multiple functions both in the tissue destruction and immune responses related to periodontal inflammation. The expression and activity of MMPs in non-inflamed periodontium is low but is drastically enhanced to pathologically elevated levels due to the dental plaque and infection-induced periodontal inflammation. Soft and hard tissue destruction during periodontitis and peri-implantitis are thought to reflect a cascade of events involving bacterial virulence factors/enzymes, pro-inflammatory cytokines, reactive oxygen species and MMPs. However, recent studies suggest that MMPs can also exert anti-inflammatory effects in defence of the host by processing anti-inflammatory cytokines and chemokines, as well as by regulating apoptotic and immune responses. MMP-inhibitor (MMPI)-drugs, such as doxycycline, can be used as adjunctive medication to augment both the scaling and root planing-treatment of periodontitis locally and to reduce inflammation systematically. Furthermore, MMPs present in oral fluids (gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), mouth-rinses and saliva) can be utilized to develop new non-invasive, chair/bed-side, point-of-care diagnostics for periodontitis and dental peri-implantitis.

Cytokines↗
PubMed2006

Effect of FGF and polylactide scaffolds on calvarial bone healing with growth factor on biodegradable polymer scaffolds.

Repair of bone defects remains a major concern in reconstructive surgery. Synthetic biodegradable polymers have been used as scaffolds for guided bone regeneration. Fibroblast growth factors (FGFs) promote cell growth, differentiation, and tissue maintenance factors. They can stimulate the proliferation of osteogenic cells and chondrocytes, and also promote angiogenesis. Acidic and basic fibroblast growth factors (FGF-1 and FGF-2, respectively) are the best known members of this protein family. To evaluate the healing of experimental bone defects using poly-L/D-lactide (PLDLA) 96/4 scaffolds and FGF-1, 18 adult rats were operated on. A 6-mm diameter critical size defect (CSD) was made in the calvarial bone of each rat. The animals were divided into three treatment groups: 1) Neither scaffold nor FGF was used (control group); 2) scaffold only; and 3) scaffold with FGF-1. Follow-up time was eight weeks. Samples were embedded in methylmethacrylate and 5-microm thick sections from the middle of each specimen were stained with modified Masson-Goldner method. The shape and size of defects were evaluated radiologically. New bone formation was measured histologically and histomorphometrically. Radiologically, in the control group the shape of the defects changed from round to oval and edges were blunt. In the other groups the defects were round with sharp edges. Histomorphometrically, mean surface area of bone trabeculae was 1.05 mm (SD +/- 0.25) in group 1 (no implant), 1.35 mm (SD +/- 0.52) in group 2 (implant) and 0.79 mm (SD +/- 0.34) in group 3 (implant and FGF-1). Histological examinations revealed no or little osteoid in the groups 1 and 2, whereas in the group 3 samples had little or moderate new bone formation. Accordingly, no clear benefit of using knitted PLDLA scaffolds combined with FGF-1 on the healing of calvarial critical size defects in rats could be demonstrated.

Animals↗
PubMed2006

Solitary angiokeratoma of the tongue.

Angiokeratoma is a rare, cutaneous vascular disorder that can occur in several clinically distinct conditions. It usually presents as multiple, red to blue or black, asymptomatic papules on the skin. Oral mucosal involvement is common in the systemic form, but very rare in the localized forms of angiokeratomas. We report the second case of a solitary papular angiokeratoma of the oral cavity.

Angiokeratoma↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

Chemically modified tetracyclines (CMT-3 and CMT-8) enable control of the pathologic remodellation of human aortic valve stenosis via MMP-9 and VEGF inhibition.

OBJECTIVE: Tetracycline derivatives affect many cellular functions relevant to chronic cardiovascular pathologies, including cell proliferation, migration and matrix remodelling. Accordingly, we sought to determine whether they may modulate the pathologic characteristics known to be significantly involved in human aortic valve stenosis, such as gelatinase production, apoptosis, expression of vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-alpha). METHODS: The effects of tetracycline derivatives (tetracycline and CMTs-3, -5, -8) on MMP-2 and -9 and their endogenous tissue inhibitor (TIMP-1 and -2) production profiles in explanted human aortic valve pieces were examined by means of gelatine zymography and reverse zymography. Chemiluminescent ELISA was performed to assess VEGF and TNF-alpha concentrations in the medium, and in order to evaluate programmed cell death, in situ labelling of the 3'-ends of the DNA fragments generated by apoptosis-associated endonucleases was performed. RESULTS: CMT-3 and -8 lowered the MMP-9 and VEGF levels significantly in a drug-, dose-, and time-dependent manner. MMP-2 and TIMPs remained unchanged, emphasizing the specificity of CMTs to MMP-9 production on the one hand and restoring the beneficial equilibrium of MMP-9 and TIMPs on the other. Tetracycline was the only drug with a significant impact on net gelatinolytic activity, suggesting that the effect of tetracycline is more extensive concerning total MMP activity. CONCLUSIONS: Tetracycline derivatives may have therapeutic effects on the pathologic remodellation of advanced human aortic stenosis through the inhibition of MMP-9 and VEGF production.

Aortic Valve Stenosis↗
PubMed2005

Levels of matrix metalloproteinase-2, -9 and -8 in the skin, serum and saliva of smokers and non-smokers.

Smoking induces skin ageing, affects wound healing and inflammatory responses in skin and mucous membranes but the mechanisms behind these adverse effects of smoking are not clear. The objective was to elucidate the mechanisms of smoking-related tissue damage, by comparing the levels of matrix metalloproteinases (MMPs) -2, -9, and -8 in the skin, serum and saliva of smokers and non-smokers. The study population consisted of 47 current smokers and 51 non-smokers, all males of Finnish origin. Skin samples from the upper inner arm were frozen in liquid nitrogen. Levels of MMP-2 and MMP-9 protein in the skin were assessed by zymography and MMP-8 isoforms were determined by Western blotting. From the serum samples, MMP-2 and MMP-9 were assessed by zymography and MMP-8 levels by time-resolved immunofluorometric assay (IFMA). From the salivary samples, MMP-8 levels were analysed by IFMA and MMP-9 levels by capture activity assay. In skin tissue, lower levels of both the pro and active forms of MMP-9 and of the active forms of MMP-8 were found in the smokers compared to the non-smokers. In serum, higher levels of proMMP-2 and proMMP-9 were found in the smokers compared to the non-smokers (P=0.001 and P<0.001, respectively), whereas MMP-8 levels did not differ significantly between the groups. Active forms of MMP-9 and MMP-2 could not be found in serum. In saliva, the amount of total MMP-9 was significantly lower in the smokers (156.0 U/ml) compared to the non-smokers (223.9 U/ml, P=0.032), whereas the levels of MMP-8 or active MMP-9 did not differ significantly between the groups. We conclude that smoking alters the levels of matrix metalloproteinases in skin tissue, serum and saliva, which may affect the turnover of extracellular matrix of skin even though the clinical impact of our findings is not clear.

Finland↗
PubMed2005

Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases.

Endostatin, a potent inhibitor of endothelial cell proliferation, migration, angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin formation from human collagen XVIII by several MMPs in vitro. The generation of endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage sites were located in the protease-sensitive hinge region between the trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show any significant activity against the C-terminus of collagen XVIII. The anti-proliferative effect of the 20-kDa endostatin, three longer endostatin-containing fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF-stimulated human umbilical vein endothelial cells was established. The anti-migratory potential of some of these fragments was also studied. In addition, production of endostatin fragments between 24-30 kDa by human hepatoblastoma cells was shown to be due to MMP action on type XVIII collagen. Our results indicate that certain, especially cancer-related, MMP family members can generate biologically active endostatin-containing polypeptides from collagen XVIII and thus, by releasing endostatin fragments, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis.

Amino Acid Sequence↗
PubMed2005

Human mesenchymal stem cell derived osteoblasts degrade organic bone matrix in vitro by matrix metalloproteinases.

Some recent studies have suggested that cells of mesenchymal origin might participate in the organic bone matrix dissolution. In the present study, collagen synthesis and degradation by human mesenchymal stem cell (MSC) derived cells were studied at early stage of osteoblast differentiation using a special two-stage in vitro culture model. In this model, cells were cultured on bovine bone slices, which were first resorbed by osteoclasts. Synthesis of type I collagen was markedly enhanced when mesenchymal cells were cultured on bone matrix. After thorough osteoclast removal, MSC derived cells were capable of degrading the organic bone matrix, and caused a release of type I collagen degradation product (ICTP) into the culture medium. This was inhibited by matrix metalloproteinase (MMP) inhibitor, while cysteine proteinase inhibitor or estrogen had no inhibitory effect. Western blot analysis or gelatin zymography confirmed the presence of MMP-2, -8, -13 and -14, but not MMP-1 or -9, in the differentiated cells. 17beta-Estradiol was found to increase the expression of MMP-2 and -14 by these cells. Finally, scanning electron microscopy showed that the differentiating human MSCs were capable of degrading organic bone matrix remnants from the bottom of the resorption lacunae. These data support the hypothesis that collagen cleavage by the same cells that are subsequently responsible for bone formation is MMP mediated process and is an important step coupling bone formation into bone resorption.

Animals↗
PubMed2005

Analysis of gene and protein expression in healthy and carious tooth pulp with cDNA microarray and two-dimensional gel electrophoresis.

Complementary DNA (cDNA) microarray and two-dimensional (2-D) gel electrophoresis, combined with mass spectrometry, enable simultaneous analysis of expression patterns of thousands of genes, but their use in pulp biology has been limited. Here we compared gene and protein expression of pulp tissues from sound and carious human teeth using cDNA microarray and 2-D gel electrophoresis to evaluate their usefulness in pulp biology research and to identify the genes with changes in carious teeth. The cDNA microarray revealed several differentially expressed genes and genes with a high expression in both tissues. These genes have various functions, e.g. effects on vascular and nerve structures, inflammation, and cell differentiation. Variability between cDNA hybridizations indicates that the overall gene expression pattern may vary significantly between individual teeth. The 2-D gel electrophoresis revealed no change between healthy and diseased tissue. The identification of 96 proteins in the pulp tissue revealed none of the gene products with corresponding high/different mRNA expression in cDNA microarray. Interestingly, we detected also a hypothetical protein (putative nucleoside diphosphate kinase), and present therefore the first evidence for the existence of this protein. Even though the methods reveal potentially important gene expression, they may currently have only limited value in in vivo pulp biology research.

Adolescent↗
PubMed2004

Segment-specific but pathologic laminin isoform profiles in human labial salivary glands of patients with Sjogren's syndrome.

OBJECTIVE: To assess the laminins in basement membrane of the labial salivary glands of patients with Sjogren's syndrome (SS) and healthy controls. METHODS: Labeling of laminin alpha1-alpha5, beta1, beta2, gamma1, and gamma2 chains was performed using immunohistochemistry with chain-specific monoclonal antibodies and pattern recognition analysis of the labeled specimens. RESULTS: Laminin alpha1, alpha2, and alpha4 chains were detected exclusively in the acinar basement membranes, whereas laminin alpha3, alpha5, beta1, gamma1, and gamma2 chains were also detected in ductal basement membranes. Laminin beta2 chain was not found. In patients with SS, laminin alpha1 and alpha2 chains were weakly labeled, but laminin alpha4 labeling was also intense in areas not infiltrated by lymphocytes. Pattern recognition analysis suggested that laminin alpha1, alpha2, and alpha4 chains were associated with acinar cells, myoepithelial cells, and tissue damage/repair, respectively. CONCLUSION: All salivary gland basement membranes signal through laminin 5, laminin 6, and laminin 10 trimers, but acinar basement membranes also signal through laminin 1, laminin 2, and laminin 8 trimers. Laminin alpha1 chain/laminin 1 may play a central role in the maintenance of acinar cells in healthy glands. This possibility was supported by the finding of variable expression of laminin alpha1 chain/laminin 1 in acinar basement membrane and its weak expression in SS with acinar cell atrophy. The impairment of myoepithelial laminin alpha2 chain/laminin 2 in patients with SS indicates a double defect in the acinar compartment and pathologic extracellular matrix-to-cell signaling, which may contribute to structural deterioration and functional abnormality of the exocrine glands.

Adult↗
PubMed2004

Expression of collagen XVIII and MMP-20 in developing teeth and odontogenic tumors.

Collagen XVIII is a basement membrane (BM) component, whereas MMP-20 (enamelysin) is a matrix metalloproteinase predominantly expressed in teeth. Since MMP-20 was found to degrade collagen XVIII, we studied the co-expression of these proteins in dental tissues. Collagen XVIII surrounded the developing tooth during early and late bell stages and was also present in developing enamel. Western blotting indicated that developing enamel contains collagen XVIII N-terminal fragments of the frizzled variant. Enamelysin was co-localized with collagen XVIII in the developing enamel matrix and stratum intermedium. Electron microscope analysis showed that total mineral, calcium and phosphorus contents of enamel were slightly increased in collagen XVIII null mice but the analysis revealed no visible defects in the enamel or dentin structures. In odontogenic tumors MMP-20 and collagen XVIII were co-localized in the enamel-like tumor matrix. Our results show that collagen XVIII is present in developing teeth, but its absence seems not to be critical for the development of the teeth.

Animals↗