Autocrine down-regulation of collagenase-3 in rat bone cell cultures by insulin-like growth factors
| Autor: | Ernesto Canalis, Anne M. Delany, Sheila Rydziel |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Biology Antibodies Gene Expression Regulation Enzymologic Fetus Endocrinology Insulin-Like Growth Factor II Internal medicine Matrix Metalloproteinase 13 Bone cell medicine Animals Collagenases Northern blot Insulin-Like Growth Factor I Autocrine signalling Cells Cultured Messenger RNA Osteoblasts Skull Osteoblast Molecular biology Somatomedin Rats Insulin-Like Growth Factor Binding Protein 2 medicine.anatomical_structure Cell culture Collagenase RNA Heterogeneous Nuclear medicine.drug |
| Zdroj: | Endocrinology. 137:4665-4670 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Insulin-like growth factors (IGF)-I and -II are presumed to act as autocrine regulators of bone formation. Recently, we demonstrated that IGF-I and -II inhibit bone collagen degradation and collagenase-3 synthesis in osteoblast cultures. Therefore, we tested the autocrine role of IGFs in the endogenous expression of collagenase-3 in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). Steady-state messenger RNA (mRNA) levels were determined by Northern blot analysis and collagenase concentrations in the culture medium were determined by Western immunoblot. Basal level collagenase-3 transcripts decreased in Ob cell cultures, coinciding with an increase in IGF-I and -II protein levels. Removal of the conditioned medium modestly increased collagenase-3 mRNA levels and restored the ability of exogenously added IGF-I to repress collagenase-3 transcripts. IGF neutralizing antibodies and IGF binding proteins-2 and -3 in excess increased and sustained collagenase mRNA, heterogeneous nuclear RNA, and protease levels in Ob cell cultures. In conclusion, IGF-I and -II are autocrine repressors of collagenase-3 synthesis, and this effect may contribute to their actions on the maintenance of a normal bone collagen matrix. |
| Databáze: | OpenAIRE |
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