The most fundamental function of an epithelial tissue is to act as a barrier, regulating interactions between the external environment and the body. This barrier function typically requires a contiguous cell layer but since teeth penetrate the oral epithelium, a modified barrier has evolved, called the junctional epithelium (JE). In health, the JE attaches to the tooth, sealing the inside of the body against oral micro-organisms. Breakdown of the JE barrier results in periodontal ligament (PDL) disintegration, alveolar bone resorption, and ultimately tooth loss. Using lineage tracing and DNA pulse-chase analyses, we identified an anatomical location in the JE that supported both fast- and slow-cycling Wnt-responsive stem cells that contributed to self-renewal of the tissue. Stem cells produced daughter cells with an extraordinarily high rate of turnover that maintained JE integrity for 1.4 y in mice. Blocking cell proliferation via a chemotherapeutic agent 5-fluorouracil (5-Fu) eliminated fast-cycling stem cells, which caused JE degeneration, PDL destruction, and bone resorption. Upon removal of 5-Fu, slow-cycling stem cells regenerated both the structure and barrier function of the JE. Taken together, our studies identified a stem cell population in the JE and have potential clinical implications for prevention and treatment of periodontitis.

One of the primary functions of epithelia is protection: this layer of closely aggregated cells covers most body surfaces and lines most body cavities and thus serves as the first line of defence against pathogen invasion (Presland & Dale, 2000; Schroeder & Listgarten, 2003). When this barrier function is compromised, a host of diseases result. In the oral cavity, some of the epithelia are keratinized, some have specialized sensory organs, and others produce mucus; all oral epithelia (OE), however, share a barrier function. Of all the OE, one of the most interesting to us is the epithelium which forms an attachment to teeth. Multiple features distinguish this junctional epithelium (JE) from neighbouring OE, namely: its non-keratinized nature (Atsuta et al., 2005; Schroeder & Listgarten, 1997), the presence of large intercellular spaces, its unique attachment to enamel and cementum (Listgarten, 1966), and its high mitotic activity (Skougaard, 1965). The formation of the JE occurs simultaneously with tooth eruption. Prior to penetration of the tooth into the oral cavity, the enamel epithelium flattens and transitions into a structure called the reduced enamel epithelium (REE). As the tooth breaches