The periodontium

This chapter focuses on the biology and signaling pathways that regulate the periodontium, a key target for bone loss that impacts the supporting structures for the teeth. We will discuss the interacting roles of the sclerostin-canonical Wnt, parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP), hedgehog signal, and the Bmp signaling pathway on the development and homeostasis of the mesenchymal components of the periodontium including the supporting alveolar bone, periodontal ligaments, and cementum associated with integration of the periodontal ligament. We discuss the key downstream proteins and genes of periodontium formation-tissue-nonspecific alkaline phosphate, (alpl), Ennp1, Ank, Ibsp, and Spp1-and evidence for their role as key regulators of cementogenesis and mineral formation in the context of the periodontium. Also, we include a discussion of the junctional epithelium and oral mucosa as key components of the periodontium. In particular, our focus includes the stem/progenitor cells-where they reside and their capacity to differentiate into the components of the periodontium. Molecular and mechanistic insights have been discovered with transcriptome and epigenetic analysis of periodontal stem/progenitor cells. The complex regulatory domains of the Bmp2 gene will be shown as an example. Overall, a model is presented to integrate the hedgehog, PTH/PTHrP, Wnt, and Bmp pathways in periodontal biology. New paradigms will be discussed for the treatment of periodontal disease and other major craniofacial defects.