| First Author | Blumbach K | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 9 | Pages | 6431-40 |
| PubMed ID | 22210772 | Mgi Jnum | J:298762 |
| Mgi Id | MGI:6489232 | Doi | 10.1074/jbc.M111.283119 |
| Citation | Blumbach K, et al. (2012) Dwarfism in mice lacking collagen-binding integrins alpha2beta1 and alpha11beta1 is caused by severely diminished IGF-1 levels. J Biol Chem 287(9):6431-40 |
| abstractText | Mice with a combined deficiency in the alpha2beta1 and alpha11beta1 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 alpha2beta1 or alpha11beta1 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. |
