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Ultrastructural abnormalities in cultured exostosis chondrocytes
Pauline Jackie Duke1, Dina Montufar-Solis, Richard Haynes
1The University of Texas Health Science Center at Houston, Dental Branch, Department of Orthodontics, 77225-0068, USA. jduke@mail.db.uth.tmc.edu
Ultrastructural Pathology
|May 31, 2002
Summary
Hereditary multiple exostoses (HME) is linked to EXT gene mutations affecting heparan sulfate synthesis. This study reveals cellular anomalies in HME chondrocytes, including cytoskeletal and nuclear changes, impacting bone growth.
Area of Science:
- Cell Biology
- Genetics
- Skeletal Biology
Background:
- Hereditary multiple exostoses (HME) is an autosomal dominant disorder.
- Caused by mutations in EXT1 and EXT2 genes, impacting heparan sulfate (HS) synthesis.
- HS chains are crucial for chondrocyte differentiation and signaling.
Purpose of the Study:
- To investigate additional ultrastructural anomalies in HME chondrocytes.
- To explore the role of cytoskeletal abnormalities in HME pathogenesis.
Main Methods:
- Transmission electron microscopy
- Deconvolution microscopy
- Analysis of chondrocytes in monolayer culture
Main Results:
- HME chondrocytes exhibit lobulated nuclei, shortened rER, numerous cell processes, podosomes, and atypical junctions.
- Abnormal mitochondria and reduced extracellular matrix were observed.
- Excessive microfilaments compartmentalize cytoplasm, potentially hindering organelle function and cell division.
Conclusions:
- Cytoskeletal abnormalities and surface modifications in HME chondrocytes contribute to the disorder's phenotype.
- Altered cell adhesiveness and signaling due to these changes may disrupt epiphyseal plate growth regulation.
Keywords:
Non-programmatic