ABSTRACT
Bisphosphonates is a group of inorganic pyrophosphates analogues that suppress bone resorption by inducing osteoclast inactivation, being frequently used for management of diseases affecting bone metabolism, bone metastases and bone tumors. However, since 2003 many cases describing the presence of necrotic bone exposures in the jaws have been described in patients receiving these drugs, what represent a signiï¬cant complication of bisphosphonates treatment. The overall incidence of bisphosphonate-related osteonecrosis of the jaws is low, ranging from 0.7% to 12%, mainly observed in those patients receiving intravenously treatment. Osteonecrosis of the jaws associated to oral bisphosphonate, particularly alendronate, has also been reported by a number of authors. Considering that alendronate is one of the most used drug worldwide, specially for treatment of osteoporosis, a better understanding of osteonecrosis of the jaws related to its use and how to manage these patients is extremely important. Therefore, in the current manuscript the authors aim to review the most important topics related to this pathological presentation.
Subject(s)
Alendronate/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/adverse effects , HumansABSTRACT
Cyclosporin A (CyA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Gingival overgrowth is one of the side-effects of the CyA-treatment, affecting the attached gingiva of 25-81% of treated patients. To investigate the production and activity of matrix metalloproteinases (MMPs) in the CyA-induced gingival overgrowth, 2 well-documented models were utilized: the in vivo CyA-induced rat gingival overgrowth and primary cultures of human gingival fibroblasts treated with CyA. Our results obtained from the Western blot assays demonstrated clearly that the production of MMP-1 and MMP-3 was significantly inhibited by CyA at similar concentrations found in the serum of patients undergoing CyA-treatment. Moreover, the gelatinolytic activity of MMP-2 was also reduced both in cultured fibroblasts and in the rat CyA-induced gingival overgrowth. Taken together, the data presented here suggest that these inhibitory effects may contribute to the extracellular matrix (ECM) components accumulation in the CyA-induced gingival overgrowth.
Subject(s)
Cyclosporine/pharmacology , Fibroblasts/drug effects , Gingiva/drug effects , Gingival Overgrowth/chemically induced , Matrix Metalloproteinase Inhibitors , Adult , Analysis of Variance , Animals , Blotting, Western , Cells, Cultured , Electrophoresis, Polyacrylamide Gel/methods , Extracellular Matrix/enzymology , Female , Fibroblasts/enzymology , Fibroblasts/metabolism , Gingiva/cytology , Gingiva/enzymology , Gingival Overgrowth/enzymology , Humans , Male , Matrix Metalloproteinases/biosynthesis , Rats , Rats, WistarABSTRACT
Hsps expressed on the cell surface have been associated with tumor invasiveness and used as targets for molecular surveillance. The present study utilized four human oral squamous cell carcinoma cells lines, SCC-4, SCC-9, SCC-15, SCC-25, the murine epidermoid carcinoma cell line LL/2, and primary cultures of human gingival fibroblasts to assess the cell surface expression of colligin/Hsp47, a proposed marker for malignancy. Immunoprecipitation studies following protein crosslinking revealed that Hsp47 was associated with a number of membrane proteins including the tetraspanin CD9. Cytometric analyses were performed to determine the distribution of cell surface colligin/Hsp47 during the phases of the cell cycle. These studies showed that colligin/Hsp47 was not limited to any phase of the cell cycle in epidermoid carcinoma cells. Boyden chamber tumor invasion assays and colloidal gold migration assays utilizing a reconstituted basement membrane (Matrigel), collagen type I, and laminin-5 substrates revealed that cell lines expressing constitutive high levels of colligin/Hsp47 manifested the lowest invasion and migration indices. The incorporation of antibodies against Hsps into the migration and invasion assays, likewise, increased the invasion indices and the phagokinetic migration indices. These data indicate that colligin/Hsp47 is anchored to the cell membrane in a complex with CD9 where it moderates tumor cell invasion and motility possibly by acting as a serpin protein inhibitor or as a receptor for collagen.
Subject(s)
Antigens, CD/metabolism , Carrier Proteins/metabolism , Heat-Shock Proteins/metabolism , Membrane Glycoproteins , Animals , Carcinoma, Lewis Lung/metabolism , Carcinoma, Lewis Lung/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Membrane/metabolism , Glycoproteins , HSP47 Heat-Shock Proteins , Humans , Microscopy, Fluorescence , Neoplasm Invasiveness , Precipitin Tests , Tetraspanin 29 , Tumor Cells, CulturedABSTRACT
Rabbit polyclonal antibody against mouse EHS laminin was used to investigate the distribution and composition of laminin in the rat first molar tooth germ. Immunohistochemical analysis showed that laminin is expressed in the inner and outer epithelia of the enamel organ and in small blood vessels in the dental papilla and strellate reticulum. Immunoblots revealed that tooth germ laminin differs from EHS laminin. Tooth germ laminin contains beta chains, while the alpha 1 chain is substituted by a 300-kDa chain. Two-dimensional electrophoresis analysis of tooth germ extract showed that beta chains appeared as four spots with approximate pI values of 6.6, 7.5, 7.8 and 8.5. These results indicate that more than-one type of laminin isoform is present in the first molar tooth germ. Additionally, we have shown that despite the early degradation of tooth germ basement membrane, the laminin molecule is still intact at the time of birth.
Subject(s)
Laminin/analysis , Tooth Germ/ultrastructure , Tooth, Deciduous/ultrastructure , Animals , Animals, Newborn , Antibodies , Basement Membrane/ultrastructure , Blotting, Western , Capillaries/ultrastructure , Dental Papilla/blood supply , Dental Papilla/ultrastructure , Electrophoresis, Gel, Two-Dimensional , Enamel Organ/ultrastructure , Epithelium/ultrastructure , Immunoblotting , Immunohistochemistry , Isomerism , Laminin/chemistry , Laminin/classification , Mice , Molar , Precipitin Tests , Rabbits , Rats , Rats, WistarABSTRACT
Atrophy of salivary glands may occur by ductal obstruction caused by calculus, infection or neoplastic processes, or as consequence of systemic diseases and aging. In the present work, we have used histochemical methods to study the expression of elastic and collagen fibers during experimental atrophy of the submandibular gland of mice. Glandular atrophy was accompanied by a rapid increase in collagen deposition in both septal and intralobular regions. The expression of elastic fibers was not significantly altered during atrophy: a discrete increase of elastic fibers was noted only around ductal structures. The results showed that experimental ductal obstruction is a useful in vivo model to study molecular events that take part in the remodeling of the extracellular matrix during atrophy of salivary glands.