| First Author | Shekaran A | Year | 2014 |
| Journal | Bone | Volume | 68 |
| Pages | 131-41 | PubMed ID | 25183373 |
| Mgi Jnum | J:215554 | Mgi Id | MGI:5605618 |
| Doi | 10.1016/j.bone.2014.08.008 | Citation | Shekaran A, et al. (2014) The effect of conditional inactivation of beta 1 integrins using twist 2 Cre, Osterix Cre and osteocalcin Cre lines on skeletal phenotype. Bone 68:131-41 |
| abstractText | Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The beta1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete beta1 integrin knockout results in embryonic lethality, studies of beta1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that beta1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of beta1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of beta1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and osteocalcin-Cre lines to generate conditional beta1 integrin deletions, where Cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific beta1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific beta1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of beta1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that beta1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while beta1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic chondryocyte-lineage cells regulate incisor eruption and perinatal bone formation in both intramembranously and endochondrally formed bones in young, rapidly growing mice. In contrast, the osteocalcin-specific beta1 integrin deletion had only minor effects on skeletal phenotype. |
