Dwarfism in Mice Lacking Collagen-binding Integrins α2β1 and α11β1 Is Caused by Severely Diminished IGF-1 Levels
| Autor: | Ralf Hallinger, Beate Eckes, Bengt F. Belgardt, Katrin Blumbach, Thomas Krieg, Jens C. Brüning, Markus Schubert, Donald Gullberg, Markus Schmitz, Harald W.A. Ehlen, Anja Niehoff, Jan-Niklas Schulz |
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| Rok vydání: | 2012 |
| Předmět: |
musculoskeletal diseases
Male endocrine system congenital hereditary and neonatal diseases and abnormalities Integrins medicine.medical_specialty Receptors Collagen endocrine system diseases medicine.medical_treatment Integrin Medizin Glycobiology and Extracellular Matrices Dwarfism Biology Growth Hormone-Releasing Hormone Biochemistry Bone and Bones Mice Bone Density Internal medicine medicine Animals Homeostasis Insulin-Like Growth Factor I Receptor Molecular Biology Osteoblasts Growth factor food and beverages Osteoblast Cell Biology Growth hormone–releasing hormone medicine.disease Mice Mutant Strains Extracellular Matrix Mice Inbred C57BL Endocrinology medicine.anatomical_structure Liver Hypothalamus Growth Hormone biology.protein Female Collagen Integrin alpha2beta1 Signal Transduction Hormone |
| Zdroj: | Journal of Biological Chemistry. 287:6431-6440 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.283119 |
| Popis: | Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis. |
| Databáze: | OpenAIRE |
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