Insulin-like growth factor I has independent effects on bone matrix formation and cell replication

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-122-1-254· OSTI ID:5562834

Hock, J M; Centrella, M; Canalis, E

The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of (2,3-/sup 3/H)proline and (methyl-/sup 3/H)thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on (/sup 3/H)proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on (/sup 3/H)thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis.

• Research Organization: Veterans Administration Medical Center, Newington, CT
• OSTI ID: 5562834
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 122:1; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
AZINES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BONE CELLS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL CULTURES
CELL DIVISION
CELL NUCLEI
COLLAGEN
CONNECTIVE TISSUE CELLS
DNA REPLICATION
GROWTH FACTORS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HORMONES
INSULIN
KINETICS
LABELLED COMPOUNDS
MAMMALS
MITOGENS
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PROLINE
PROTEINS
PYRIMIDINES
PYRROLES
PYRROLIDINES
RATS
REACTION KINETICS
RIBOSIDES
RODENTS
SCLEROPROTEINS
SOMATIC CELLS
SYNTHESIS
THYMIDINE
TRITIUM COMPOUNDS
VERTEBRATES