Gene therapy for osteoinduction

Various disorders of bone and mineral metabolism are diagnosed to be defective in genes related to cellular growth and differentiation. Gene therapy to introduce normal copy of defective genes into cells and tissues to compensate for silent, minimally expressed or mutated genes can be accomplished by multiple approaches. Although each bone disease/disorder would require a case-wise evaluation of potential strategies for best possible outcome, considerations for the gene therapy approaches are: 1) introduction of a therapeutic gene into cells without changing any of its native biological properties, 2) minimal or total absence of immunogenic and toxic effects from introduced vectors, genetically-modified cells or conditionally-expressed proteins, while achieving a therapeutic effect, 3) cell-type or tissue-specific, regulated expression of a therapeutic protein, and 4) restricting or abolishing the expression of disease triggering genes at the RNA or DNA levels. Although most of the currently available therapies for osteoinduction are pharmacological in nature, molecular understanding of biologically-driven factors provides greater opportunity to test their potential as therapeutic proteins. Strategies of gene therapy complement this approach through efficient delivery of genes encoding therapeutic proteins to target sites. The present review will attempt to give a comprehensive account of existing therapies for osteoinduction and discuss the potential and limitation of vector-mediated gene therapy for bone diseases.