The genetic functional matrix theory

Abstract

AIM: Based on an extensive literature review, the functional matrix hypothesis was revisited in the nineties by Moss. In his series of publications, interactions between epigenetic processes and cells and their products leading to morphogenesis were considered to be responsible for ‘all cranial development’. Completion of ‘the genome project’ provided an opportunity to examine the validity of the ‘functional matrix theory’ through the use of microarray technology, real time RT-PCR and knock out gene technology. Due to the enormity of the task at hand, it was decided to begin by examining ‘condylar growth’. Bone fracture healing is a common experimental model to study natural bone growth. Similarly, it was demonstrated that condylar growth induced by mandibular advancement mirrored natural growth. Thus mandibular advancement offers a good model to study condylar growth. It was, therefore, decided to carry out micro-array analysis of thousands of genes expressed during condylar natural growth, and during growth induced by mandibular advancement. In this way, interactions between epigenetic and genetic factors could be studied. MATERIALS AND METHOD: Two hundred and eighty rats were divided into seven experimental (advancement) and seven control groups. The rats were sacrificed at different time points and total RNA was extracted for microarray and RT-PCR. The analysis was limited to genes that showed a 2 or more fold change using ‘gene spring’ software. RESULTS: Six hundred and twenty four genes showed a significant change between groups. Knock out genes of five different identified genes demonstrated either absence or major impairment of skeletal tissues, while normal growth of soft tissues was evident. CONCLUSION: Genes play a fundamental role in modulating condylar growth. Levels of expression of these genes are influenced by the surrounding functional matrix. Evidence is therefore provided to warrant a renaming to 'The genetic functional matrix theory'.