Reconciling the roles of FAK in osteoblast differentiation, osteoclast remodeling, and bone regeneration.

Integrins link the inside of a cell with its outside environment and in doing so regulate a wide variety of cell behaviors. Integrins are well known for their roles in angiogenesis and cell migration but their functions in bone formation are less clear. The majority of integrin signaling proceeds through focal adhesion kinase (FAK), an essential component of the focal adhesion complex.

Skeletal phenotype of growing transgenic mice that express a function-perturbing form of beta1 integrin in osteoblasts.

Skeletal modeling entails the deposition of large amounts of extracellular matrix (ECM) to form structures tailored to withstand increasing mechanical loads during rapid growth. Specific ECM molecules bind to integrin receptors on the cell surface, thereby triggering a cascade of signaling events that affect critical cell functions. To evaluate the role of integrins during skeletal growth, transgenic mice were engineered to express a function-perturbing fragment of beta1 integrin consisting of the transmembrane domain and cytoplasmic tail under the control of the osteocalcin promoter (TG mice).

Effects of disrupted beta1-integrin function on the skeletal response to short-term hindlimb unloading in mice.

The study was designed to determine whether beta1-integrin plays a role in mediating the acute skeletal response to mechanical unloading. Transgenic (TG) mice were generated to express a dominant negative form of beta1-integrin under the control of the osteocalcin promoter, which targets expression of the transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice were subjected to hindlimb unloading by tail suspension for 1 wk.