CAREER: The Effect of Mechanical Loading History on Gene Expression During Distraction Osteogenesis

Rutgers, The State University Of New Jersey-Rbhs-New Jersey Med, Newark NJ

Investigators

Abstract

9985500 Harten The objective of this proposal is to examine the effect of specific mechanical loading conditions on the expression of genes critical to the bone repair process. A rabbit distraction osteogenesis model coupled with highly controlled loading conditions will serve as the experimental model for this study. The genetic analysis will consist of quantitative reverse transcription polymerase chain reaction (RT-PCR) to assess differences in gene expression, and in situ hybridization studies to localize the cells responsible for producing the genes. Further analyses examining cellular proliferating patterns, histological changes, as well as alterations in the downstream mechanical and micromechanical properties of the regenerating tissues will be performed. Finally, an analytical dynamic finite element model will be developed to predict the loading conditions in the tissues in response to the different loading protocols. These results will be compared to the experimental data in order to formulate the relationships between tissue level stresses and strains and the production of genes that are key to the process of bone repair. Integrated with this research plan are specific educational goals. The PI intends to enhance his current orthopaedic resident teaching activities by incorporating new presentation media, develop new courses for the medical student curriculum at his institution, and continue with the development of new biomedical engineering courses at Rutgers University. The proposed research plan will also strengthen these teaching activities by providing a real world context to the basic science material covered in these courses. Additionally the proposed research plan will provide research opportunities for at least 3 graduate students. The skills and education gained by the students through this experience will be invaluable as they prepare to enter the biomedical job market. This research plan will also provide educational opportunities for at least three other groups of individuals. Medical students and residents will also be involved with the execution of these experiments. The experience gained by these individuals will become very important for them as they progress to the next step in their education. Local high school students will also benefit from this research activity. Through a program run by the New Jersey Medical School, students from minority districts who have been identified as having "college potential" are given the opportunity to work in a research setting. This project will support at least two of these young people per year over its four year timeline. Through the synthesis of the data generated in the various aspects of the study, the objective of this research project is to refine our current concepts regarding the mechanobiology of bone. At present, our understanding of this phenomenon is very qualitative. The ultimate goal of this project is to develop quantifiable relationships that may be used to predict and regulate the bone formation process. Such algorithms may be useful in understanding and treating clinical pathologies, as well as advancing the basic science of skeletal tissue differentiation.