Ultrastructural Abnormalities in Cultured Exostosis Chondrocytes
| Autor: | Jacqueline T. Hecht, Pauline Jackie Duke, Richard Haynes, Dina Montufar-Solis |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Hereditary multiple exostoses
Biology Microfilament Chondrocyte Pathology and Forensic Medicine Extracellular matrix chemistry.chemical_compound Chondrocytes Structural Biology medicine Humans Cells Cultured Germ-Line Mutation Actin Cell Nucleus Organelles Bone growth Heparan sulfate medicine.disease Extracellular Matrix Cell biology medicine.anatomical_structure chemistry Biochemistry Cytoplasm Female Exostoses Multiple Hereditary |
| Zdroj: | Ultrastructural Pathology. 26:99-106 |
| ISSN: | 1521-0758 0191-3123 |
| DOI: | 10.1080/01913120252959272 |
| Popis: | Hereditary multiple exostoses (HME) is an autosomal dominant disorder characterized by inappropriate chondrocyte proliferation and bone growth arising at the juxtaepiphyseal region of the long bones. HME is caused by mutations in the EXT 1 and EXT 2 genes, which have glycosyltransferase activity. These genes are responsible for synthesis of heparan sulfate (HS) chains, which are important signaling molecules in chondrocyte differentiation. HME chondrocytes in monolayer culture have been shown by transmission electron and deconvolution microscopy to contain enormous bundles of actin, cross-linked with muscle specific alpha-actinin. Here additional ultrastructural anomalies in HME chondrocytes are reported, including lobulated nuclei, shortened channels of rER, large numbers of cell processes and podosomes, nontypical junctions, elongated, bulbous-ended mitochondria, and reduced extracellular matrix. Microfilaments are present throughout the cytoplasm, compartmentalizing it, and isolating organelles. The excess microfilaments, attributed to increased cell adhesiveness, are likely to interfere with secretion and cytokinesis, and sterically hinder intracellular organelle differentiation. The observed surface modifications and cytoskeletal abnormalities are proposed to play a role in development of the mutant phenotype, via changes in cell adhesiveness and/or binding of signals to receptors, which results in loss of the unidirectionality of growth in the epiphyseal plate. |
| Databáze: | OpenAIRE |
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