Biochemical Composition

Four mineralized tissues are found in the oral cavity, and three of these—enamel, dentin, and cementum—are components of the tooth. Their characteristics and biochemical composition are summarized in Table 1-1. The composition of cementum is similar to that of bone. Cementum is approximately 45% to 50% hydroxyapatite by weight and the remaining portion is collagen and noncollagenous matrix proteins. Type I collagen is the predominant collagen of cementum (constitutes up to 90% of the organic components in cellular cementum); in cellular intrinsic fiber cementum, just as in bone, it accommodates mineral deposition. Type I collagen is also the major collagen within the PDL region, and its main function is to structure the fiber bundles that anchor the tooth to the bone and distribute masticatory forces. Other collagens associated with cementum include type III, a less cross-linked collagen found in high concentrations during development and during repair and regeneration of mineralized tissues but is reduced with maturation of this tissue, and type XII collagen, a fibril-associated collagen with interrupted triple helices that binds to type I collagen and to noncollagenous proteins. Type XII collagen is found in high concentrations in ligamentous tissues, including the PDL, with lower levels noted in cementum. This nonfibrillar collagen interacts with type I collagen and may assist in maintaining a functional and mature PDL that can withstand the forces of occlusion. Trace amounts of other collagens, including types V, VI, and XIV, also are found in extracts of mature cementum; however, these may be contaminants from the PDL region, produced by PDL fibroblasts associated with collagen fibers inserted into cementum. Noncollagenous proteins identified in cementum also are associated with bone and include the following: alkaline phosphatase, bone sialoprotein, dentin matrix protein 1, dentin sialoprotein, fibronectin, osteocalcin, osteonectin, osteopontin, proteoglycans, proteolipids, tenascin, and several growth factors. Enamel proteins also have been suggested to be present in cementum but not yet convincingly demonstrated. Two apparently unique cementum molecules, an adhesion molecule (cementum attachment protein) and an insulin-like growth factor have been identified, but further studies are warranted to confirm the existence and function of these molecules. The recent finding that cementoblasts can express the osteoblast-specific membrane protein bone restricted ifitm-like protein (Bril, a member of interferon inducible transmembrane protein family) adds additional support for similarity between these two cells.

Initiation of Cementum Formation

Although cementum formation takes place along the entire root, its initiation is limited to the advancing root edge (Figure 9-3). At this site, Hertwig’s epithelial root sheath (HERS), which derives from the coronoapical extension of the inner and outer enamel epithelium (see Chapter 5), is believed to send an inductive message, possibly by secreting some enamel proteins or other epithelial product, to the facing ectomesenchymal pulp cells. These cells differentiate into odontoblasts and produce a layer of predentin (Figures 9-4 and 9-5). The next series of events results in formation of cementum on the root surface; however, the specific cells and trigger factors responsible for promoting its formation still are unresolved. Current theories include the following: (1) Soon after, HERS becomes interrupted, and ectomesenchymal cells from the inner portion of the dental follicle then can come in contact with the predentin; (2) infiltrating dental follicle cells receive a reciprocal inductive signal from the dentin and/or the surrounding HERS cells and differentiate into cementoblasts; or (3) HERS cells transform into cementoblasts (a process discussed subsequently). During these processes, some cells from the fragmented root sheath form discrete masses surrounded by a basal lamina, known as epithelial cell rests of Malassez, which persist in the mature PDL (Figure 9-6; see also Figure 9-5). Evidence is increasing that these rests are not simply residual cells but instead may participate in maintenance and regeneration of periodontal tissues. If some HERS cells remain attached to the forming root surface, they can produce focal deposits of enamel-like material called enamel pearls (Figure 9-7), most commonly found in the area of furcation of roots.

Origin of Periodontal Cells and Differentiation of Cementoblasts

Several fundamental issues still need to be determined to better understand the periodontium, including the following:

Answers to these questions are important not only to understand normal formation processes but also to envisage novel, targeted therapeutic approaches for periodontal diseases.

The long-standing view is that precursor cells for cementoblasts and PDL fibroblasts reside in the dental follicle and that factors within the local environment regulate their ability to function as cementoblasts that form root cementum or as fibroblasts of the PDL. Cells involved in regenerating periodontal tissues include stem cells migrating from the vascular region, as well as local progenitor cells. The precise location of the progenitor cells and whether there exists a common progenitor or distinct progenitors for each cell type remain to be defined. In addition, there is now increasing evidence that epithelial cells from HERS may undergo epithelial-mesenchymal transformation into cementoblasts during development. Such transformation is a fundamental process in developmental biology that occurs, among other processes, as we have seen during neural crest cell migration and medial edge fusion of the palatal shelves. Structural and immunocytochemical data support the possibility that at least in part cementoblasts are transformed from epithelial cells of HERS. In rodents, initial formation of acellular cementum takes place in the presence of epithelial cells, and some studies have shown that enamel organ–derived cells are capable of producing mesenchymal products, such as type I collagen, bone sialoprotein, and osteopontin.

Uncertainty still exists as to whether acellular (primary) and cellular (secondary) cementum are produced by distinct populations of cells expressing spatiotemporal behaviors that result in the characteristic histologic differences between these tissues. This potential cellular and formative distinctiveness is highlighted in mice null for tissue nonspecific alkaline phosphatase gene or rats treated with bisphosphonates. In these animals, acellular cementum formation is affected significantly, whereas cellular cementum appears to develop normally. In hypophosphatemic mice, formation of acellular cementum can be rescued by enzyme replacement therapy for tissue nonspecific alkaline phosphatase. This suggests differences in cell types or factors controlling development of these two varieties of cementum. In the human counterpart, hypophosphatasia, characterized by low levels of alkaline phosphatase, cementum formation appears to be limited or nonexistent, not exclusive to acellular versus cellular. In contrast, in mice with mutations in genes that maintain extracellular pyrophosphate levels, such as ank and PC-1, resulting in limited levels of pyrophosphate, one sees formation of cellular cementum even at early stages of root development. These findings suggest an important role for phosphate in controlling the rate of cementum formation.

Molecular Factors Regulating Cementogenesis

To understand the specific role of phosphate and other molecules, additional studies that focus on defining the cells and factors controlling development, maintenance, and regeneration of periodontal tissues are required. Some of the factors known to be involved in controlling these events are discussed next and are summarized in Table 9-1.

Acellular Extrinsic Fiber Cementum (Primary Cementum)

Cementoblasts that produce acellular extrinsic fiber cementum differentiate in proximity to the advancing root edge. During root development in human teeth, the first cementoblasts align along the newly formed but not yet mineralized mantle dentin (predentin) surface following disintegration of HERS (Figure 9-8, A and B). The cementoblasts exhibit fibroblastic characteristics, extend cell processes into the unmineralized dentin, and initially deposit collagen fibrils within it so that the dentin and cementum fibrils intermingle. Mineralization of the mantle dentin starts internally and does not reach the surface until mingling has occurred. Mineralization then spreads across into cementum under the regulatory influence of noncollagenous matrix proteins, thereby establishing the cementodentinal junction. In rodents, initial cementum deposition occurs onto the already mineralized dentin surface, preventing the intermingling of fibers (see Figure 9-3, A).