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Dihydrocytochalasin B Enhances Transforming Growth Factor-β-Induced Reexpression of the Differentiated Chondrocyte Phenotype without Stimulation of Collagen Synthesis
- Source :
- Experimental Cell Research. 204:268-277
- Publication Year :
- 1993
- Publisher :
- Elsevier BV, 1993.
-
Abstract
- Rabbit articular chondrocytes were treated with retinoic acid (RA) to eliminate the differentiated phenotype marked by the synthesis of type II collagen and high levels of proteoglycan. Exposure of such cells to transforming growth factor-beta 1 (TGF-beta 1) in secondary culture under serum-free and RA-free, defined conditions led to reexpression of the differentiated phenotype. The microfilament modifying drug, dihydrocytochalasin B (DHCB), enhanced the effectiveness of TGF-beta 1 and produced a threefold stimulation of type II collagen reexpression (measured by 2-D CNBr peptide mapping) at 0.3 ng/ml TGF-beta 1 without altering total collagen synthesis. Type II collagen reexpression was maximal from 1 to 5 ng/ml TGF-beta 1, with or without DHCB. The effect of DHCB on proteoglycan synthesis was maximal at 1 ng/ml TGF-beta 1. At this dose TGF-beta alone produced no increase in 35SO4 incorporation, while simultaneous treatment with DHCB caused a sevenfold stimulation of proteoglycan synthesis. DHCB-independent stimulation proteoglycan reexpression occurred between 5 and 15 ng/ml TGF-beta 1. In contrast, TGF-beta 1-dependent stimulation of proteoglycan synthesis in differentiated chondrocytes in primary monolayer culture was not substantially affected by DHCB. The collagen data suggest that TGF-beta 1 utilizes separate pathways to control phenotypic change and collagen (matrix) synthesis. Microfilament modification by DHCB selectively enhances the effectiveness of the TGF-beta 1-dependent signaling pathway that controls reexpression of the differentiated phenotype.
- Subjects :
- Cartilage, Articular
medicine.medical_specialty
Cytochalasin B
Type II collagen
Retinoic acid
Tretinoin
Stimulation
Microfilament
Culture Media, Serum-Free
Chondrocyte
chemistry.chemical_compound
Transforming Growth Factor beta
Internal medicine
medicine
Animals
Cells, Cultured
Dose-Response Relationship, Drug
biology
Cartilage
Cell Differentiation
Cell Biology
Cell biology
Actin Cytoskeleton
Phenotype
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Proteoglycan
chemistry
biology.protein
Proteoglycans
Collagen
Rabbits
Signal Transduction
Transforming growth factor
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 204
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....bf4e6ef911c926f473a12407a54ae1f7