Project 442815

Oral health is of fundamental importance for humans and the two most common disorders of humans, periodontal diseases and dental caries, both localize to the oral cavity. For periodontal diseases, the connective tissues of tooth-supporting structures play critically important functions in maintaining and enabling the attachment of the teeth to the jaws and essential for chewing and masticatory function. Currently we do not have a clear understanding of how periodontal diseases cause breakdown of the connective tissues that support the teeth but what is known is that uncontrolled overgrowth and stiffening of connective tissue matrices are strongly associated with these disorders. In this proposal we will examine how an ion channel, TRPV4, which is present in cells of gum tissues that are called fibroblasts, regulates the ability of these cells to properly remodel and ensure that the form and function of connective tissues is maintained. Notably, mutations of the gene for TRPV4 causes 4 different diseases that affect connective tissue form and function. We don't understand how TRPV4 contributes to the regulation of connective tissues in gum tissues. We will examine at the molecular, cellular and tissue levels, how this channel, contributes to the regulation and maintenance of normal gum tissue structure and functions and what are the important determinants of TRPV4 that affect connective tissues and the maintenance of gum health. Knowledge from this project could suggest new approaches for the treatment of gum diseases, which affect over 30% of the adult North American population.