Biomedical subjects

Gaston Godeau

Publications and source records attributed to Gaston Godeau.

At least 19 recordsLinked to original sources

PubMed2007

Comparison of extracellular matrix in skin and saphenous veins from patients with varicose veins: does the skin reflect venous matrix changes?

Varicose vein disease is a frequently occurring pathology with multifactorial causes and a genetic component. An intense remodelling of the varicose vein wall has been described and could be at the origin of its weakness and altered elasticity. We have described previously a dysregulation of collagen synthesis in cultured smooth muscle cells from saphenous veins and in dermal fibroblasts from the skin of patients with varicose veins, suggesting a systemic defect in their connective tissue. The present study describes comparative morphological and immunohistochemical data in both the skin and saphenous veins of eight control subjects (undergoing coronary bypass surgery) and eight patients with varicose veins. Histological staining of glycoproteins, the elastic fibre network and collagen bundles showed that the remodelling and fragmentation of elastic fibres observed in varicose veins were also present in the skin of the patients. When compared with control subjects, we observed in both the veins and skin of patients with varicose veins (i) an increase in the elastic network, as quantified by image analysis; (ii) an accumulation of collagen type I, fibrillin-1 and laminin; and (iii) an overproduction of MMP (matrix metalloproteinase)-1, MMP-2 and MMP-3, analysed by immunohistochemistry, but normal levels of other MMPs (MMP-7 and MMP-9) and their inhibitors (TIMP-1, TIMP-2 and TIMP-3). An imbalance of extracellular matrix production/degradation was thus observed in veins as well as in the skin of the patients with varicose veins and, taken together, these findings show that remodelling is present in different organs, confirming systemic alterations of connective tissues.

Adult↗

PubMed2006

Epigallocatechin gallate's protective effect against MMP7 in recessive dystrophic epidermolysis bullosa patients.

The analysis of phenotype-genotype correlations of patients suffering from recessive dystrophic epidermolysis bullosa (RDEB) evidenced intrafamilial and interfamilial phenotype variability occurring for the same mutation of COL7A1; this underscores the role of other genetics environmental factors in the expressivity of the disease. In this work, we checked whether matrilysin 1 (matrix metalloproteinase (MMP)7) could take part in the epidermal detachment in RDEB. Furthermore, we investigated epigallocatechin 3 gallate (EGCG) to determine whether it could inhibit matrilysin activities on collagen type VII and fibrillin 1 known to be associated with the dermo-epidermal junction. In this work, matrilysin 1 was detected in affected and unaffected skins of the three RDEB patients; furthermore, MMP7 was shown to degrade ex vivo on healthy normal skin collagen VII and fibrillin 1. Thus, we suspect that MMP7 could take an active part in the epidermal detachment occurring during RDEB. We evidenced that EGCG in in vitro as well as in ex vivo experiments was a good inhibitor of MMP7 and developed a good protection of collagen type VII and fibrillin 1 susceptible of being degraded by MMP7. We therefore propose that EGCG could be used beneficially in patients suffering from RDEB.

Adult↗

PubMed2006

Do Langerhans cells behave similarly in elderly and younger patients with chronic periodontitis?

OBJECTIVE: The purpose of this study was to compare the number, the distribution and the expression of markers of maturation of Langerhans cells (LC) in elderly and younger patients with chronic periodontitis in order to evidence the effect of aging on LC in inflammatory gingival tissue. METHODS: Gingival tissue specimens presenting chronic periodontitis from 8 elderly patients aged >75 (group E) and from 8 younger patients aged 50-60 (considered as controls, group C) were used for immunohistochemistry with monoclonal antibodies against CD45RB (leucocytes), CD1a (LC), markers of LC maturation (DC-LAMP, CD83) and number of immunolabelled cell subsets was evaluated using image analysis. RESULTS: The difference in the number of CD45RB+ leucocytes in the upper connective tissue between groups was not significant. In group E, the number of CD1a+ LC was significantly decreased (P<0.002) in the epithelium and significantly increased (P<0.0004) in the upper connective tissue. Furthermore, in group E, intraepithelial CD1a+ LC are more often observed in the upper epithelium and their dendritic processes were shorter and less numerous. Concerning the expression of markers of maturation, the numbers of intraepithelial DC-LAMP+ cells and CD83+ cells were significantly increased (P<0.0007 and P<0.02, respectively) in group E. CONCLUSION: During chronic periodontitis in elderly patients, the decrease in the number of intraepithelial LC and the alteration of dendritic processes could be balanced by a cellular distribution often observed in the upper epithelium associated with changes in cell maturation in response to bacterial elements.

Age Factors↗

PubMed2006

Dense fibrillar collagen matrices: a model to study myofibroblast behaviour during wound healing.

Fibroblastic cells play an important part in wound healing. Human dermal fibroblasts seeded onto three-dimensional fibrillar collagen matrices migrate into the collagen network and differentiate into myofibroblasts. In order to evaluate the use of collagen matrices as model systems for studying myofibroblast phenotype during wound healing, myofibroblast behaviour migrating into dense or loose matrices was compared. The effect of collagen concentration on cell morphology, remodelling, proliferation and apoptosis of human myofibroblasts was evaluated. Myofibroblasts within dense collagen matrices (40 mg/ml) were spindle shaped, similar to cells observed during tissue repair. In contrast, cells within loose matrices (5mg/ml) were more rounded. Matrix hydrolysis activities (MT1-MMP and MMP2) did not differ between the two collagen concentrations. The myofibroblast proliferation rate was measured after 24h bromodeoxyuridine incorporation (BrdU). Cells in dense collagen matrices proliferated at a higher rate than cells in loose matrices at each culture time point tested. For example, 40% of cells in dense matrices were replicating compared to 10% of cells in loose matrices after 28 days in culture. Apoptotic cells were only detected in dense matrices from day 21 onwards when cells had already migrated into the collagen network. Taken together, these results show that a high collagen concentration has a stimulatory effect on myofibroblast proliferation and apoptosis, two important events in wound healing. Thus, dense matrices can be used to create controlled conditions to study myofibroblast phenotype.

Apoptosis↗

PubMed2006

Dextran derivatives modulate collagen matrix organization in dermal equivalent.

Dextran derivatives can protect heparin binding growth factor implied in wound healing, such as transforming growth factor-beta1 (TGF-beta1) and fibroblast growth factor-2 (FGF-2). The first aim of this study was to investigate the effect of these compounds on human dermal fibroblasts in culture with or without TGF-beta1. Several dextran derivatives obtained by substitution of methylcarboxylate (MC), benzylamide (B) and sulphate (Su) groups were used to determine the effects of each compound on fibroblast growth in vitro. The data indicate that sulphate groups are essential to act on the fibroblast proliferation. The dextran derivative LS21 DMCBSu has been chosen to investigate its effect on dermal wound healing process. Fibroblasts cultured in collagenous matrices named dermal equivalent were treated with the bioactive polymer alone or associated to TGF-beta1 or FGF-2. Cross-sections of dermal equivalent observed by histology or immunohistochemistry, demonstrated that the bioactive polymer accelerates the collagen matrices organization and stimulates the human type-III collagen expression. This bioactive polymer induces apoptosis of myofibroblast, property which may be beneficial in treatment of hypertrophic scar. Culture media analyzed by zymography and Western blot showed that this polymer significantly increases the secretion of zymogen and active form of matrix metalloproteinase-2 (MMP-2), involved in granulation tissue formation. These data suggest that this bioactive polymer has properties which may be beneficial in the treatment of wound healing.

Actins↗

PubMed2005

Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis.

Fucoidans are sulfated fucosylated polymers from brown algae cell wall that exhibit some heparin/heparan sulfate properties. We previously demonstrated that these polysaccharides were able in vitro to stimulate dermal fibroblast proliferation and extracellular matrix deposition. Here, we investigated the action of a 16kDa fucoidan fraction on parameters involved in connective tissue breakdown. This fucoidan is able to inhibit gelatinase A secretion and stromelysin 1 induction by interleukin-1beta on dermal fibroblasts in culture. Furthermore, we observed that fucoidan increases the rate of association of MMPs with their specific inhibitors namely TIMPs. Using tissue sections of human skin in ex vivo experiments, we evidenced that this polysaccharide was able to minimize human leukocyte elastase activity resulting in the protection of human skin elastic fiber network against the enzymatic proteolysis due to this serine proteinase. These results suggested that fucoidan could be used for treating some inflammatory pathologies in which uncontrolled extracellular matrix degradation takes place.

Cells, Cultured↗

PubMed2005

Collagen and elastin cross-linking: a mechanism of constrictive remodeling after arterial injury.

Constrictive remodeling after arterial injury is related to collagen accumulation. Cross-linking has been shown to induce a scar process in cutaneous wound healing and is increased after arterial injury. We therefore evaluated the effect of cross-linking inhibition on qualitative and quantitative changes in collagen, elastin, and arterial remodeling after balloon injury in the atherosclerotic rabbit model. Atherosclerotic-like lesions were induced in femoral arteries of 28 New Zealand White rabbits by a combination of air desiccation and a high-cholesterol diet. After 1 mo, balloon angioplasty was performed in both femoral arteries. Fourteen rabbits were fed beta-aminopropionitrile (beta-APN, 100 mg/kg) and compared with 14 untreated animals. The remodeling index, i.e., the ratio of external elastic lamina at the lesion site to external elastic lamina at the reference site, was determined 4 wk after angioplasty for both groups. Pyridinoline was significantly decreased in arteries from beta-APN-treated animals compared with controls, confirming inhibition of collagen cross-linking: 0.30 (SD 0.03) and 0.52 (SD 0.02) mmol/mol hydroxyproline, respectively (P = 0.002). Scanning and transmission electron microscopy showed a profound disorganization of collagen fibers in arteries from beta-APN-treated animals. The remodeling index was significantly higher in beta-APN-treated than in control animals [1.1 (SD 0.3) vs. 0.8 (SD 0.3), P = 0.03], indicating favorable remodeling. Restenosis decreased by 33% in beta-APN-treated animals: 32% (SD 16) vs. 48% (SD 24) (P = 0.02). Neointimal collagen density was significantly lower in beta-APN-treated animals than in controls: 23.0% (SD 3.8) vs. 29.4% (SD 4.0) (P = 0.004). These findings suggest that collagen and elastin cross-linking plays a role in the healing process via constrictive remodeling and restenosis after balloon injury in the atherosclerotic rabbit model.

Aminopropionitrile↗

PubMed2005

Fibroblast populated dense collagen matrices: cell migration, cell density and metalloproteinases expression.

Dense collagen matrices obtained by using the property of type I collagen to form liquid crystals at high concentrations, were shown to be colonized by human dermal fibroblasts (Biomaterials 23 (2002) 27). In order to evaluate them as possible tissue substitutes, we investigated in this study the mechanism of cell colonization. Fibroblasts were seeded at the surface of collagen matrices at concentrations of 5 and 40 b mg/ml. Cell density and migration were estimated from histological sections over 28 days within 500 microm thick matrices. At day 14, migration started in the 40 mg/ml matrices, attaining 320 microm in distance and 5500 cell/mm(3) in density at day 28. As zymography and western blot techniques demonstrated production of collagenase 1 (MMP1) and gelatinase A (MMP2) in culture medium, collagen hydrolysis was required for cells to penetrate the collagen network. Furthermore, the presence of MMP1 and MMP2 and their tissue inhibitors TIMP1 and TIMP2 was revealed by immunohistochemistry. We presently show that 40 mg/ml collagen matrices are colonized by human dermal fibroblasts and reach, at day 28, a density close to that measured in human dermis.

Adult↗

PubMed2005

Electrical activity alterations induced by chronic absorption of lindane (gamma-hexachlorocyclohexane) trace concentrations in adult rat heart.

The heart of adult rat offspring, born to mothers treated with trace concentrations of lindane (0.5 to 2 ppb) through a beverage and to mothers chronically treated with lindane (CL-T) with the same trace concentration, also through a beverage, during lactation and growth has a round shape and accumulates lindane. The left ventricle (LV) presents a hypertrophied area, atrophied papillary muscles, and unorganized collagen bundles and layers. These observations led us to study the electrical activity of their left ventricle papillary muscles (LVPM) by recording action potential using intracellular microelectrodes. CL-T shortened LVPM action potential duration (APD): 1 ppb shortened the plateau; 2 ppb shortened the plateau and the slow repolarizing phase. In CL-T (2 ppb) and untreated groups, low temperature (22 degrees C) decreased the resting potential and prolonged APD. TEA (tetraethylammonium; 1-2 mmol/L) partially lengthened CL-T (2 ppb lindane) APD. Quinidine (0.2 mmol/L) and E-4031 (10 nmol/L) prolonged CL-T APD, suggesting that the rapid delayed outward K+ current (IKr) was increased. Our results indicate the silent effects of chronic exposure to trace concentrations of lindane on the morphological and electrical activity of heart muscle. They demonstrate that chronic lindane treatment of female rats alters the tissue integrity and electrical activity in the LV of their offspring.

Action Potentials↗

PubMed2005

Lupinus albus, a novel vegetable extract with metalloproteinase inhibitory properties: a potential periodontal therapy.

BACKGROUND: In this study we examine the properties of a vegetable extract from seeds of Lupinus albus (LU 105). In previous works we demonstrated that LU 105 reduced the expression, by gingival fibroblasts, of both matrix metalloproteinase (MMP)-2 and MMP-9. We decided to study the impact of LU 105 on cell proliferation and morphology. Using organ culture media we also studied the MMP and tissue inhibitors of metalloproteinases (timp) expression AND THE cytokines secretion. METHODS: Healthy and inflamed gingival biopsies were placed in appendage culture with or without LU 105. The organ culture media were analyzed using Western blottings (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, TIMP-1, and TIMP-2) and gelatine zymography. A reverse transcription polymerase chain reaction (RT-PCR) was also performed on healthy and inflamed gingival biopsies, which were maintained in culture with or without LU 105 0.1%. Then, we decided to determine the amount of cytokines present in the organ culture media such as interleukin (IL)-1 beta, IL-4, IL-6, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF)-alpha. RESULTS: When gingival biopsies derived from inflamed tissues were cultured with LU 105 0.1% in the culture media, the MMP and TIMP expression and activity decreased significantly when compared to cultures without LU 105. Moreover, we did not note any statistical difference in the cell proliferation compared with human gingival fibroblast cultures without LU 105. Furthermore, IL-1 beta, IL-6, TGF-beta, and TNF-alpha amounts in the culture media decreased significantly, whereas IL-4 increased significantly when LU 105 0.1% was added to the culture media. CONCLUSION: LU 105, a novel metalloproteinase inhibitor with few consequences on cell proliferation and morphology, is a vegetable extract with potential clinical capacity.

Analysis of Variance↗

PubMed2004

Activation of latent transforming growth factor beta 1 and inhibition of matrix metalloprotease activity by a thrombospondin-like tripeptide linked to elaidic acid.

Impaired wound healing and skin aging are characterized by neutral protease-mediated destruction of matrix macromolecules associated with disturbance in tissue repair. We synthesized a fatty acyl-peptide derivative at aims to simultaneously activate latent TGF-beta through its peptide domain, KFK, and inhibit MMPs through its lipophilic moiety, elaidic acid. Elaidyl-KFK as well as KFK were shown to activate LAP-TGF-beta both in vitro, using a solid phase assay with immobilized LAP-TGF-beta, and ex vivo using human dermal fibroblasts cultures. In both assays, as much as up to 10% of LAP-TGF-beta added could be recovered as active form. KQK, KQFK as well as their lipopeptide counterparts were inactive. Elaidyl-KFK-mediated LAP-TGF-beta activation led to up-regulation of collagen and TIMP-1 production and down regulation of PMA-induced MMP-1 expression in fibroblasts cultures. Those effects could be suppressed by supplementing cell culture medium with blocking TGF-beta antibody. Elaidyl-KFK inhibited MMP-2, MMP-9, MMP-3, MMP-1, in vitro with IC(50) equal to 1.2, 1.0, 0.24 and 8.9 microM, respectively. Its ex vivo inhibitory capacity, as assessed using skin tissue sections, towards the elastin-degrading capacity of MMP-9 was even more pronounced. At a 1 microM concentration, the lipopeptide decreased by up to 80% enzyme activity. Thus, "Lipospondin," i.e. elaidyl-KFK might be considered as a promising model compound to prevent age-associated dermal alterations.

Adolescent↗

PubMed2004

An engineered biopolymer prevents mucositis induced by 5-fluorouracil in hamsters.

Oral mucositis is a common, treatment-limiting, and costly side effect of cancer treatments whose biological underpinnings remain poorly understood. In this study, mucositis induced in hamsters by 5-fluorouracil (5-FU) was observed after cheek-pouch scarifications, with and without administration of RGTA (RG1503), a polymer engineered to mimic the protective effects of heparan sulfate. RG1503 had no effects on 5-FU-induced decreases in body weight, blood cell counts, or cheek-pouch and jejunum epithelium proliferation rates, suggesting absence of interference with the cytotoxic effects of 5-FU. Extensive mucositis occurred in all of the untreated animals, and consisted of severe damage to cheek pouch tissues (epithelium, underlying connective tissue, and muscle bundles). Only half of the RG1503-treated animals had mucositis, over a mean area 70% smaller than in the untreated animals. Basement membranes were almost completely destroyed in the untreated group but was preserved in the RG1503 group. RG1503 blunted or abolished the following 5-FU-induced effects: increases in matrix metalloproteinase (MMP)-2, MMP-9, and plasmin, and decreases in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These data indicate that mucositis lesions are related to massive release of proteolytic enzymes and are improved by RG1503 treatment, this effect being ascribable in part to restoration of the MMP-TIMP balance. RG1503 given with cancer treatment might protect patients from mucositis.

Animals↗

PubMed2004

Effect of a dextran derivative associated with TGF-beta1 or FGF-2 on dermal fibroblast behaviour in dermal equivalents.

Dextran derivatives that mimic the action of heparin have been shown to protect heparin-binding growth factors, such as Transforming Growth Factor-beta1 (TGF-beta1) and Fibroblast Growth Factor-2 (FGF-2). The aim of this study was to investigate the effect of LS21 DMCBSu, a dextran derivative which contains methylcarboxylate, benzylamide and sulfate groups, both by itself and when combined with TGF-beta1 and FGF-2, on the behaviour of fibroblasts. Two systems were assessed: a monolayer culture and three-dimensional collagenous matrices (dermal equivalent). Polymeric biomaterial LS21 DMCBSu and LS21 DMCBSu associated with either TGF-beta1 or FGF-2, were added to the monolayer culture on day 3. After 7 days of culture the number of cells was determined. Two treatments were carried out on the dermal equivalents: 9 days of treatment from day 0 to day 9 of culture and 9 days of treatment from day 21 to day 30 of culture for the premature and the mature dermal equivalents respectively. In the monolayer culture, the bioactive polymer produced a slight increase in fibroblast growth (10% with 10 microg/ml of LS21 DMCBSu) and promoted the stimulating effect of the growth factors on cell growth. In the premature dermal equivalents growth was stimulated by 20% when 10 microg/ml LS21 DMCBSu was added. The dextran derivative mixed with TGF-beta1 slightly inhibited the growth effect of the growth factor in the dermal equivalents. The functionalized dextran with FGF-2 enhanced the stimulating effect of the growth factor in the premature dermal equivalent. A significant increase in cell growth was observed with the fibroblasts treated with the FGF-2 LS21 DMCBSu mixture and FGF-2 (51% and 40%, respectively). However, none of the described treatments affected the cell growth in the mature dermal equivalent. Furthermore, the dextran derivative had no effect on dermal contraction under these experimental conditions (3D culture).

Cell Differentiation↗

PubMed2003

Langerin+ versus CD1a+ Langerhans cells in human gingival tissue: a comparative and quantitative immunohistochemical study.

Langerhans cells (LC) are dendritic cells of the immune system able to capture intraepithelial pathogens and migrate to regional lymph nodes to present them to naive T cells. Up to now immunohistological studies on human gingival LC have been carried out using antibodies against HLA-DR or CD1a molecules. A new marker of LC called Langerin (CD207) and described, among other subcellular localisations, in the Birbeck granules is now available in immunohistochemistry. The purpose of this in situ study was to quantify and to compare Langerin+ versus CD1a+ LC number in order to show differences in the expression of these molecules, if any, and to determine which marker is the most specific. The present study was conducted using nine frozen healthy gingival samples. Double immunofluorescence procedures were performed with an anti-Langerin antibody revealed by FITC and with an anti-CD1a-PE antibody. Mounted slides were analysed by fluorescence microscopy and quantifications were performed on projected slides associated with a grid of 0.015 mm(2). Our results have shown that 1/ the number of CD1a+ LC was significantly increased (P=0.01) when compared with Langerin+ LC 2/ 92% of Langerin+ LC co-expressed CD1a 3/ only 82% of CD1a+ cells co-expressed Langerin 4/ a positive correlation was noted between CD1a+ and Langerin+ LC numbers. The present study has revealed the heterogeneity in the phenotype of gingival LC population and shown that Langerin seems the most specific marker for the study of LC.

Adolescent↗

PubMed2003

Effect of adenovirus-mediated overexpression of decorin on metalloproteinases, tissue inhibitors of metalloproteinases and cytokines secretion by human gingival fibroblasts.

Decorin is a small leucine-rich proteoglycan that plays a role in control of cell proliferation, cell migration, collagen fibrillogenesis and modulation of the activity of TGF-beta. In the present study, we investigated the effects of decorin on the production of metalloproteinases (MMP-1, -2, -3, -9 and -13), tissue inhibitors of metalloproteinases (TIMP-1, -2) and cytokines (TGF-beta, IL-1beta, IL-4 and TNF-alpha). Decorin was overexpressed in cultured human gingival fibroblasts using adenovirus-mediated gene transfer. Decorin infection resulted in decreased protein levels of MMP-1 and MMP-3 whereas MMP-2 and TIMP-2 secretion was increased. MMP-9, MMP-13 and TIMP-1 were not affected by decorin infection. Cytokine measurements by ELISA showed that decorin overexpression reduced TGF-beta and IL-1beta. In contrast, IL-4 and TNF-alpha levels were markedly increased in decorin-infected cells. These results suggest that decorin could modulate the expression of certain metalloproteinases and their inhibitors, as well as the production of cytokines. Altogether, our data suggest that decorin might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation.

Adenoviridae↗

PubMed2003

Skin expression of metalloproteinases and tissue inhibitor of metalloproteinases in sibling patients with recessive dystrophic epidermolysis and intrafamilial phenotypic variation.

A number of COL7A1 mutations have now been reported in recessive dystrophic epidermolysis bullosa patients, and the analysis of phenotype-genotype correlations showed evidence for interfamilial and intrafamilial phenotypic variability, occurring for the same mutation. Collagenase and stromelysin activities have been found to be overexpressed in skin cultures of some recessive dystrophic epidermolysis bullosa patients, and tissue destruction in the disease process might result from an imbalance of metalloproteinases (MMP) over tissueinhibitor of metalloproteinases (TIMP). So we suspected that the phenotypic variability for the same mutation could be linked to other genetic or environmental factors, as a particular balance between MMP and TIMP. Organ cultures were performed using explants from the skin of three patients from the same family with recessive dystrophic epidermolysis bullosa to reveal and quantify the expression of MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1), TIMP-1, and TIMP-2, and to compare the results with those obtained with two human control skins, with the same experimental conditions. Increased amounts of all metalloproteinases investigated were observed in the skin of the three recessive dystrophic epidermolysis bullosa affected sibling brothers, both in lesioned and in apparently nonlesioned skin, compared with controls. The amounts of MMP-1, MMP-2, MMP-3, and MMP-9 increased particularly in the skin of the more clinically affected patient. Furthermore for this patient we evidenced higher amounts of MMP-1 and also a lower TIMP-1 amount in his unlesioned and lesioned skin compared with the other two affected patients and with healthy control donors. So we can suspect that recessive dystrophic epidermolysis bullosa phenotypic variability could be related to patients' collagenase activity heterogeneity, linked to imbalance between MMP-1 and TIMP-1.

Adolescent↗

PubMed2003

Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D.

OBJECTIVE: To evaluate the dental effects of 1-hydroxylated vitamin D3 treatment in patients with familial hypophosphatemic vitamin D-resistant rickets. Study design Forty-eight children and adult patients were included in the study; 16 had received no treatment or phosphate supplements with vitamin D/25-(OH) D3 before puberty. The 32 younger ones had received phosphate supplements with 1alpha-(OH)D3 from infancy. All patients were clinically examined, and panoramic and periapical radiographs were made. Evaluations of decayed, missing, or filled teeth and decayed or filled teeth indexes and of pulp ratios allowed comparison with healthy age-matched control patients. RESULTS: Poor dental health and characteristic dental anomalies were found in the 16 older patients. In contrast, the 32 younger patients had a normal dental status as regards reference ranges in healthy age-matched populations, although they still showed prominent pulp horns on deciduous teeth and increased pulp area/tooth area ratios. CONCLUSIONS: This investigation shows the beneficial effects of 1alpha-(OH)D3 treatment on the dental status of vitamin D-resistant rickets patients and emphasizes the necessity of early treatment. Remaining defects may result from early exposure of odontoblasts and surrounding osteoblasts to hypophosphatemia, before the commencement of treatment, and/or from intrinsic cell disturbances linked to the genetic alteration(s).

Adolescent↗

PubMed2003

Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy and diseased human gingiva.

BACKGROUND: The purpose of this study was to quantify the amount of matrix metalloproteinases such as MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and MMP-13 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 expressed by human gingival explants in culture media and the area fraction (AA%) of gingival collagen fibers according to the degree of inflammation, to investigate a possible correlation between these enzymes and collagen loss. METHODS: Gingival tissue specimens from 6 healthy controls (group 1), 17 patients with mild gingival inflammation (group 2), 10 patients with moderate gingival inflammation (group 3), and 9 patients with severe gingival inflammation (group 4) were placed in organ culture for 3 days. The MMPs and TIMPs in the culture media were quantified using zymography, dot blotting, and Western blotting. Paraffin gingival sections were stained with sirius red F3Ba for visualization of collagen fibers, then the area fraction (AA%) occupied by the gingival fibers was determined by automated image analysis. RESULTS: The AA% occupied by collagen fibers significantly decreased from group 1 (53%) to group 4 (35%). The decrease in collagen fibers was inversely correlated with the significant increase in MMP-1, MMP-9, and MMP-13 (dot blotting analysis), with the increase of the active form of MMP-2, and with the active form and proform of MMP-9 (zymography analysis). CONCLUSION: The present study showed that metalloproteinases, particularly MMP-2, MMP-9, MMP-1, and MMP-13, are involved in the gingival extracellular matrix degradation during periodontitis.

Blotting, Western↗