The role of integrins in bone homeostasis.

In the Gullberg and Eckes laboratories unique reagents to integrins have been developed which are now being applied to bone biology. The current application is aimed at facilitating a regular exchange between the laboratories to strengthen the just star ted project. As a starting point we have studied the distribution of the integrins alpha2 and alpha11 in bone. In accordance with earlier published data alpha11 is found in periosteal fibroblasts whereas alpha2 is mainly expressed on endothelial cells. A preliminary study in the Eckes laboratory has revealed that absence of alpha11 and alpha2 integrins leads to reduced mineral density in the long bones of adult mice. Studies of mechanical properties, geometrical parameters, ability to tolerate maxim um load and deformation, all point in the direction of collagen-binding integrins being involved in bone structure, and thus justify studies of the role of collagen-binding integrins in osteoporosis. In the project we aim to : - further characterize bon e in the mouse models, - establish model systems of cell adhesion and matrix turnover from primary mouse osteoblasts and periosteal fibroblasts from wild-type mice and genetically engineered mice lacking both alpha2 and alpha11 integrins, - set up a model system based on co-culture in 3D collagen gels to study the effect of periosteal fibroblasts on osteoblast mineralization. One hypothesis is that mechanical stain in the periosteum in an integrin-dependent paracrine mechanism influence bone mineralizatio n, and that these interactions might be attenuated in osteoporosis.