Cytokine gene therapy in bone remodeling

The use of gene transduction to explore cytokine over-expression in the control of bone metabolism and remodeling has increased researchers' understanding of certain cytokine biological function in vivo as well as being a potential for therapeutic purposes. Experimentation with a number of vector technologies has provided more information on the characteristics and activities of different vectors and their payload genes within the bone environment. This has enabled progress in refining the use of gene transduction for bone disease. The potential for bone morphogenic proteins (BMPs) and osteoprotegerin (OPG) prolonged overexpression is still to be explored in greater detail for diseases requiring net bone deposition and repair. Although there have been fewer studies that specifically look at gene transduction of cytokines for treatment of bone cancer, certainly those that examine effects of OPG show promise, and current clinical trials with OPG-Fc protein will help to pave the way for addressing safety in future studies involving long-term OPG therapy. A role of OPG in inhibiting the immune function through its ability to modify APC/T cell interaction is still an issue in treatments where immuno-modulation is contraindicated. Clearly, other molecules may emerge with the potential in modulation of bone metabolism through gene transduction approaches. There are still considerable unknowns in the exploration of the maximization of the effectiveness for gene therapeutic approaches in bone disease. © 2010 Elsevier Inc. All rights reserved.