Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation

Journal Article · Thu Apr 05 04:00:00 EDT 1990 · Journal of Biological Chemistry; (USA)

OSTI ID:6870939

Kato, Y; Iwamoto, M ^[1]

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1. Osaka Univ. (Japan)

The effects of basic fibroblast growth factor (bFGF) on terminal differentiation of chondrocytes and cartilage-matrix calcification were investigated. Rabbit growth-plate chondrocytes maintained as a pelleted mass in a centrifuge tube produced an abundant proteoglycan matrix during the matrix-maturation stage, yielding a cartilage-like tissue. Thereafter, they terminally differentiated to hypertrophic chondrocytes which produced high levels of alkaline phosphatase. These cells induced extensive calcification of the matrix in the absence of additional phosphate. Addition of bFGF to the chondrocyte cultures abolished the increases in alkaline phosphatase activity, {sup 45}Ca deposition, and the calcium content. These effects were dose-dependent, reversible, and observed in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. The inhibitory effects could be observed only when chondrocytes were exposed to bFGF in a transition period between the matrix-maturation and hypertrophic stages. As chondrocytes differentiated to hypertrophic cells, bFGF became less effective in inhibiting the expression of the mineralization-related phenotypes. The present study also shows that although the rate of ({sup 35}S)sulfate incorporation into large, chondroitin sulfate proteoglycan in the cell-matrix fraction is very high during the matrix-maturation stage, it abruptly decreases by 90% after terminal differentiation. Furthermore, the terminal differentiation-associated decrease in proteoglycan synthesis was delayed by bFGF. These results provide evidence that bFGF inhibits terminal differentiation of chondrocytes and calcification.

• OSTI ID: 6870939
• Journal Information: Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 265:10; ISSN JBCHA; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550801 -- Morphology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE PHOSPHATASE
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BODY
CALCINOSIS
CALCIUM 45
CALCIUM ISOTOPES
CARTILAGE
CATTLE
CELL DIFFERENTIATION
CONNECTIVE TISSUE
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
ESTERASES
EVEN-ODD NUCLEI
FIBROBLASTS
FUNCTIONS
GLYCOPROTEINS
GROWTH FACTORS
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MITOGENS
NUCLEI
NUCLEIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PHENOTYPE
PHOSPHATASES
PROTEINS
RABBITS
RADIOISOTOPES
RUMINANTS
SOMATIC CELLS
SULFATES
SULFUR 35
SULFUR COMPOUNDS
SULFUR ISOTOPES
TISSUES
TRACER TECHNIQUES
VERTEBRATES