The extracellular matrix (ECM) of cementum resembles other mineralized tissues in composition; however, its physiology is unique, and it contains molecules that have not been detected in other tissues. Cementum components influence the activities of periodontal cells, and they manifest selectivity toward some periodontal cell types over others. In light of emerging evidence that the ECM determines how cells respond to environmental stimuli, we hypothesize that the local environment of the cementum matrix plays a pivotal role in maintaining the homeostasis of cementum under healthy conditions. The structural integrity and biochemical composition of the cementum matrix are severely compromised in periodontal disease, and the provisional matrix generated during periodontal healing is different from that of cementum. We propose that, for new cementum and attachment formation during periodontal regeneration, the local environment must be conducive for the recruitment and function of cementum-forming cells, and that the wound matrix is favorable for repair rather than regeneration. How cementum components may regulate and participate in cementum regeneration, possible new regenerative therapies using these principles, and models of cementoblastic cells are discussed.
