Chemokine RANTES/CCL5 as an unknown link between wound healing in the jawbone and systemic disease: is prediction and tailored treatments in the horizon?

Abstract

Background: This research elucidates the question of whether common and widespread dental procedures (DP) like root filling (RF) and the removal of wisdom teeth (WT) contribute to chronic inflammation in the jawbone. Dentists, in carrying out these DP, can set off defective wound healing in the jawbone in ignorance of its connection to inflammatory mediators and the possibility of it being a hidden cause of chronic systemic diseases (SYD).

Materials and methods: We examined samples of the jawbone for seven cytokines by multiplex analysis in three groups of jawbone areas. In order to clarify systemic interrelations, specimens from 16 patients were analyzed in areas of former surgery in the retromolar wisdom tooth area; specimens from 16 patients were analyzed in the jawbone, apically of teeth with RF; and specimens from 19 patients were of the healthy jawbone. Each of the retromolar and the apical jawbone samples showed clinically fatty degenerated and osteonecrotic medullary changes.

Results: All fatty necrotic and osteolytic jawbone (FDOJ) samples showed regulated on activation, normal T-cell expressed and secreted (RANTES) and fibroblast growth factor (FGF)-2 as the only extremely overexpressed cytokines. FDOJ cohorts showed a 30-fold mean overexpression of RANTES and a 20-fold overexpressed level of FGF-2 when compared to healthy controls.

Conclusions: As RANTES is discussed in the literature as a possible contributor to inflammatory diseases, and though it might have oncogenic effects, we hypothesize that FDOJ in areas of improper and incomplete wound healing in the jawbone might act as hyperactivated signaling pathways, while serving as an unknown source of "silent inflammation". Because of the wide range of RANTES in immune diseases, treating FDOJ can cover many potential prediction or prognosis of individual outcomes.

Keywords: Chronic inflammation in the jawbone; Fatty necrotic osteolytic jawbone; Hyperactivated signaling pathways; Predictive preventive personalized medicine; RANTES/CCL5.

Figure 1

FDOJ sample of fatty and osteolytic degenerated bone marrow (left part) and a contrast medium in the FDOJ cavity after curettage (right part).

Figure 2

Photomicrograph of an FDOJ lesion with typical signs of osteonecrosis and fatty degenerated and necrobiotic adipocytes, centered in a hollow cavitation of the jawbone. The red circle shows fatty degenerated and necrobiotic adipocytes centered in a hollow cavitation of the jawbone with clear signs of osteonecrosis (1:200).

Figure 3

Distribution of seven cytokines in HJB (n = 19) (pg/mL) and in FDOJ (n = 16).

Figure 4

FDOJ sample from the former area of WTS with focal loss of medullary bone structure, as well as fatty changes in the remaining osteoporotic marrow defect. Single bony trabeculae protrude from the softened and yellowish altered surrounding marrow tissue.

Figure 5

Distribution of seven cytokines in HJB (n = 19) (pg/mL) and in FDOJ (n = 16) from the jawbones of a group of patients with SYD and RFT.

Figure 6

Comparison of seven cytokines in FDOJ underneath RFT #47 with the cytokines in the healthy jawbone (n = 19). Intraoperative documentation of extension of FDOJ in the right lower jawbone, area #47 apically of RFT #47, by contrast agent after the surgical removal of RFT #47.

Figure 7

Comparison of the seven cytokines in the FDOJ underneath RFT #46 with the cytokines in the healthy jawbone (n = 19). The left X-ray shows the apical area of RFT #46 in a red circle on a two-dimensional orthopantomogram (2D-OPG); the right X-ray shows the same area on the sagittal plane in three-dimensional cone beam (3D-CB).

Figure 8

Comparison of seven cytokines in the FDOJ in area #48/49 with cytokines in a healthy jawbone (n = 19). The left X-ray shows the retromolar WT area on a two-dimensional orthopantomogram (2D-OPG); the right X-ray shows the same area in the sagittal plane in three-dimensional cone beam (3D-CB).