Inflammatory and immunological aspects of dental pulp repair

Abstract

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.

Fig. 1

Pulp capping with Ca(OH)₂ at day 2 (a), day 8 (b), day 15 (c) and day 30 (d). The cavity was prepared on the mesial aspect of the first maxillary molar. During pulp exposure, some dentin fragments were pushed into the pulp. The slight inflammation is resolved at day 15. A reparative dentin bridge starts to be formed at day 8 (b), and becomes thicker at days 15 and 30 (c and d). Pulp remnants and tunnels are seen even at day 30.

Fig. 2

Rat incisor pulp observed with light microscopy. The cell population is dense, heterogeneous, mostly constituted by fibroblast-like cells (pulpoblasts). Some cells are clear (arrow), whereas most others are darker.

Fig. 3

Pulp cells observed with the transmission electron microscope. Most cells display a fibroblast-like appearance. Here a cell becomes apoptotic (arrow).

Fig. 4

Macrophage (m) in a healthy pulp. Tubulo-vesicular structures are seen, forming phago-lysosomes. In the center of the cell lysosomes (ly) are implicated in the degradation and destruction of apoptotic debris and residual extracellular matrix molecules.

Fig. 5

Reactionary dentin (Rd) separated from normal dentin (d) by a calico-traumatic line (star). This dentin is formed by the odontoblasts (O), secreting collagen in the predentin (Pd). Pulp cells (p) are not implicated in the formation of this physio-pathological dentin.

Fig. 6

Reparative dentin (star) formed 15 days (a) and 30 days (b) after implantation of A-4 by differentiated pulp cells.

Fig. 7

(a) Immunoperoxidase staining of dendritic cells (brown) in the healthy human dental pulp with an anti-HLA-DR antibody. Sections were slightly counterstained with toluidine blue. V, blood vessel; P, pulp core. (b and c) Immunoperoxidase staining of T-lymphocytes (brown) in healthy and inflamed human dental pulps with an anti-CD3 antibody. In healthy tissue (b), rare T-lymphocytes are scattered within the pulp. In inflamed pulp (c), T-lymphocyte density is highly increased. Sections were slightly counterstained with toluidine blue. P, pulp core; V, blood vessel; Od, odontoblast layer. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.” has been incorporated in the caption to Fig. 7)

Fig. 8

Pulp capping with a bone sialoprotein (BSP). Preparation of the cavity and pulp exposure at day 0 (a). Moderate inflammation is seen in the pulp at day 8 after implantation of collagen pellets loaded with BSP (b). The formation of reparative dentin starts around day 15 (c). At day 30, a homogeneous atubular reparative dentin layer (star) closes totally the pulp exposure (d).

Fig. 9

Pulp cell proliferation is seen at day 8 (a) by PCNA staining in the coronal pulp near the agarose beads (b) used as carrier for A+/−4. In the root, labeling is seen in a sub-odontoblastic border at day 8. At day 15, labeling is seen near the beads, but not at direct contact (see b and d). No labeling is detectable in the root. Cells are grouped around agarose beads loaded with amelogenin isoforms resulting from spliced genes. Masson’s trichrome staining in (c), immunostaining for PCNA in (d), showing that proliferating cells are located near the beads. The cells differentiate toward a osteoblast/odontoblast phenotype, as shown by osteopontin (OPN) immunostaining (e); bar = 100 μm.

Fig. 10

Effects of pulp capping with A+4 (a) and A−4 (b–d). Whereas A+4 induces mostly the formation of reparative dentin (star), A − 4 firstly stimulate the formation of a reparative dentin bridge (b and d), and afterward stimulate the closure of the lumen of the root canal (c). b = beads; bar = 100 μm.