Insulin-Like Growth Factor-I Is Essential for Embryonic Bone Development
| Autor: | Shigeki Nishida, Yongmei Wang, S. B. Doty, Daniel D. Bikle, Takeshi Sakata, Bernard P. Halloran, Hashem Z Elalieh, Wenhan Chang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Indian hedgehog Cellular differentiation medicine.medical_treatment Dwarfism Bone and Bones Chondrocyte Mice Insulin-like growth factor Calcification Physiologic Chondrocytes Endocrinology Internal medicine medicine Animals Insulin-Like Growth Factor I Collagen Type II Cell Proliferation Mice Knockout Bone Development biology Reverse Transcriptase Polymerase Chain Reaction Growth factor Parathyroid Hormone-Related Protein Cell Differentiation biology.organism_classification medicine.disease Spinal column Microscopy Electron Phenotype medicine.anatomical_structure Osteocalcin biology.protein |
| Zdroj: | Endocrinology. 147:4753-4761 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2006-0196 |
| Popis: | Although IGF-I has been identified as an important growth factor for the skeleton, the role of IGF-I on embryonic bone development remains unknown. Here we show that, in IGF-I-deficient (IGF-I−/−) mice, skeletal malformations, including short-limbed dwarfism, were evident at days post coitus (dpc) 14.5 to 18.5, accompanied by delays of mineralization in the spinal column, sternum, and fore paws. Reduced chondrocyte proliferation and increased chondrocyte apoptosis were identified in both the spinal ossification center and the growth plate of long bones. Abnormal chondrocyte differentiation and delayed initiation of mineralization was characterized by small size and fewer numbers of type X collagen expressing hypertrophic chondrocytes and lower osteocalcin expression. The Indian hedgehog-PTHrP feedback loop was altered; expression of Indian hedgehog was reduced in IGF-I−/− mice in long bones and in the spine, whereas expression of PTHrP was increased. Our results indicate that IGF-I plays an important role in skeletal development by promoting chondrocyte proliferation and maturation while inhibiting apoptosis to form bones of appropriate size and strength. |
| Databáze: | OpenAIRE |
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