Ngampis Six

Inflammatory and immunological aspects of dental pulp repair

The repair of dental pulp by direct capping with calcium hydroxide or by implantation of bioactive extracellular matrix (ECM) molecules implies a cascade of four steps: a moderate inflammation, the commitment of adult reserve stem cells, their proliferation and terminal differentiation. The link between the initial inflammation and cell commitment is not yet well established but appears as a potential key factor in the reparative process. Either the release of cytokines due to inflammatory events activates resident stem (progenitor) cells, or inflammatory cells or pulp fibroblasts undergo a phenotypic conversion into osteoblast/odontoblast-like progenitors implicated in reparative dentin formation. Activation of antigen-presenting dendritic cells by mild inflammatory processes may also promote osteoblast/odontoblast-like differentiation and expression of ECM molecules implicated in mineralization. Recognition of bacteria by specific odontoblast and fibroblast membrane receptors triggers an inflammatory and immune response within the pulp tissue that would also modulate the repair process.

Bone sialoprotein-induced reparative dentinogenesis in the pulp of rat's molar.

Abstract Bone sialoprotein (BSP), an osteogenic protein (OP), mixed with a carrier, was implanted in the pulp of rat first upper molars (OP group). Cavities were prepared with dental burs and pulp perforation was carried out by pressure with the tip of a steel probe. After 8, 14, and 30 days, the rats were killed and the pulps of the OP group were compared with (1) a sham group (S group), (2) a group where the carrier was implanted alone (C group), and (3) capping with calcium hydroxide (Ca group). After 8 days, a few inflammatory cells were seen, mostly located at the pulp surface near the perforation. In the Ca group, a dentin bridge started to form, in contrast to the other groups. After 15 days, globular structures were seen in the pulps of the S and C groups. A reparative osteodentin bridge isolated the pulp from the cavity in the Ca group. Variable reactions were seen in the OP group, with some evidence of cell and matrix alignments or plugs of osteodentin in continuity with an inner layer of reparative dentin. After 30 days, irregular osteodentin formation was observed in the pulps of the S and C groups, with a tendency for globular structures to merge, but with interglobular spaces filled by pulp remnants. In the Ca group, osteodentin was observed in the mesial part of the pulp chamber. In the BSP-implanted group, the osteogenic protein stimulated the formation of a homogeneous dentin-like deposit occupying most of the mesial part of the pulp. Apparently, BSP stimulates the differentiation of cells which secrete an organized extracellular matrix more efficiently than any other capping material used so far. Altogether, the results reported here support that bone sialoprotein displays novel bioactive properties and is capable of stimulating in 1 month’s time the development of a thick reparative dentinal tissue in the pulp, occluding the perforation and filling the mesial third of the pulp chamber.

Dentonin, a MEPE Fragment, Initiates Pulp-healing Response to Injury

Phosphorylated extracellular matrix proteins, including matrix extracellular phosphoprotein (MEPE), are involved in the formation and mineralization of dental tissues. In this study, we evaluated the potential of Dentonin, a synthetic peptide derived from MEPE, to promote the formation of reparative dentin. Agarose beads, either soaked with Dentonin or unloaded, were implanted into the pulps of rat molars, and examined 8, 15, and 30 days after treatment. At day 8, Dentonin promoted the proliferation of pulp cells, as visualized by PCNA-labeling. RP59-positive osteoblast progenitors were located around the Dentonin-soaked beads. PCNA- and RP59-labeling were decreased at day 15, while osteopontin, weakly labeled at day 8, was increased at 15 days, but dentin sialoprotein was undetectable at any time. At 8 days, precocious reparative dentin formation occurred in pulps containing Dentonin-soaked beads, with formation slowing after 15 days. These results suggest that Dentonin affects primarily the initial cascade of events leading to pulp healing.

Osteogenic proteins (bone sialoprotein and bone morphogenetic protein-7) and dental pulp mineralization

Bone sialoprotein (BSP) cross-linked to collagen/gelatin was implanted in the pulp of rat’s upper molars. Comparison was carried out with a sham group (non implanted), with a group of rats receiving the carrier alone, and a group of molars where the perforated pulps were capped with calcium hydroxide. The cavities were occluded with a glass-ionomer cement (GIC). After 8, 14 and 30 days respectively the rats were killed by intracardiac perfusion of the fixative and processed for light microscopy. Dentin and predentin debris pushed into the pulp during the preparation enhanced self-repair processes, with large pulp remnants. The carrier alone induced slight inflammation, and calcium hydroxide the formation of a reparative dentin bridge. BSP stimulated the recruitment of cells which produced an homogeneous atubular dentin-like structure, filling after one month the mesial third of the crown pulp. Osteogenic protein (OP-1) used in the same experimental conditions induced the formation of osteodentin in the coronal pulp and the radicular part of the pulp was totally filled by a mineralized material. The differences reported here suggest two possible different therapeutic approaches with the two osteogenic proteins, BSP inducing pulp mineralization in the crown part, and OP-1 occluding the root part of the pulp.

Dentin Extracellular Matrix Molecules Implanted into Exposed Pulps Generate Reparative Dentin : a Novel Strategy in Regenerative Dentistry

For years, dental surgeons have used calcium hydroxide as the ‘gold standard’ therapy for direct pulp-capping. Depending on the degree of bacterial contamination, pulp inflammation, and tissue degradation, the results vary.

Matricellular molecules and odontoblast progenitors as tools for dentin repair and regeneration.

This review summarizes the in vivo experiments carried out by our group after implantation of bioactive molecules (matricellular molecules) into the exposed pulp of the first maxillary molar of the rat or the mandibular incisor of rats and mice. We describe the cascade of recruitment, proliferation and terminal differentiation of cells involved in the formation of reparative dentin. Cloned immortalized odontoblast progenitors were also implanted in the incisors and in vitro studies aimed at revealing the signaling pathways leading from undifferentiated progenitors to fully differentiated polarized cells. Together, these experimental approaches pave the way for controlled dentin regenerative processes and repair.

Minéralisation de la pulpe dentaire : apports de l'ingénierie tissulaire aux thérapeutiques de demain en odontologie

When bioactive molecules such as bone sialoprotein (BSP), bone morphogenetic protein-7 (BMP-7, also termed OP-1) and chondrogenic Inducing Agents (CIA, A+4 and A-4) were implanted in the pulp of the first upper molars, mineralizations were induced. They were either limited to the formation of a reparative dentinal bridge closing the pulpal wound (CIA A+4), or filled the mesial part of the coronal pulp (BSP), or filled totally the pulp located in the root canal (BMP-7 and CIA A-4). Consequently, these molecules may change in the next future the every day practice in dentistry.