Tissue engineering holds great promise as a way of enhancing the normal regenerative potential of bone. By deconstructing the skeleton into its components and examining how each component influences the reparative response, it is clear that cells resident in bone, bioactive molecules produced by these cells and those brought into bone via the circulation and the unique extracellular matrix that makes up the bone itself are involved in a continuous and ever-changing set of reciprocal interactions during regeneration. Reviewed here is current information regarding the efficacy of 3 prominent signaling cascades that orchestrate bone formation, parathyroid hormone, Wnt and bone morphogenetic proteins, in enhancing bone repair. I suggest how we might successfully generate new bone in increasingly complex clinical situations by modulating the availability of these signals to cells already present within bone tissue.
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