title: Alteration of activity and survival of osteoblasts obtained from human periodontitis patients: role of TRAIL.
abstract: Periodontal disease (Pd) is characterized by extensive alveolar bone loss, that occurs as a consequence of the impairment of the normal bone remodelling. Bone remodelling is regulated by the correct balance between osteoclast and osteoblast formation and activity. Alveolar bone loss could be due to an increased bone resorption by osteoclasts or a decreased bone formation by osteoblasts (OBs) or both. Although the role played by osteoclasts in increasing bone resorption in Pd is already known, the behaviour of OBs in this disease is poorly understood. In the present study we hypothesized that activity and survival of OBs, locally present in alveolar bone of Pd patients, are altered. Thus, we studied the activity and survival of OBs obtained from alveolar bone fragments of Pd patients. The results, obtained in OBs from the patients were compared with those from OBs obtained from healthy donors. We demonstrated that OBs from Pd patients weakly express OB phenotype in respect to the control cells. In particular, the alkaline phosphatase activity and the collagen type I production, as well as the formation of mineralized nodules, typical markers of differentiated OBs, were significantly lower in Pd patients. Interestingly, we also demonstrated that OBs from the patients were more sensitive to the apoptotic effect induced by TNF-related apoptosis-inducing ligand (TRAIL). TRAIL, a member of the TNF superfamily, induces apoptosis by interacting with its death receptors, (DR4, DR5). However, its activity can be modulated by two decoy receptors, DcR1 and DcR2. Thus, the sensitiveness of TRAIL induced apoptosis is determined by the ratio of death and decoy receptor. We demonstrated that OBs from Pd patients showed an imbalanced ratio between death and decoy TRAIL receptors due to the down-regulation of DcR2 expression. Furthermore, the levels of TRAIL in the serum of the same patients were significantly higher than those detected in the controls. In conclusion, we show for the first time that the alveolar bone loss in Pd patients could be due to the increased TRAIL-mediated apoptosis of OBs.
authors.affiliation: Department of Human Anatomy and Histology, University of Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mori
authors.forename: G
authors.initials: G
authors.lastname: Brunetti
authors.forename: S
authors.initials: S
authors.lastname: Colucci
authors.forename: F
authors.initials: F
authors.lastname: Ciccolella
authors.forename: M
authors.initials: M
authors.lastname: Coricciati
authors.forename: P
authors.initials: P
authors.lastname: Pignataro
authors.forename: A
authors.initials: A
authors.lastname: Oranger
authors.forename: A
authors.initials: A
authors.lastname: Ballini
authors.forename: D
authors.initials: D
authors.lastname: Farronato
authors.forename: F
authors.initials: F
authors.lastname: Mastrangelo
authors.forename: S
authors.initials: S
authors.lastname: Tetè
authors.forename: F R
authors.initials: FR
authors.lastname: Grassi
authors.forename: M
authors.initials: M
authors.lastname: Grano
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001842:Bone and Bones / Q000473:pathology; D002113:Calcification, Physiologic; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010518:Periodontitis / Q000097:blood / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood / Q000494:pharmacology*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D053221:TNF-Related Apoptosis-Inducing Ligand; C451501:TNFRSF10D protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D000469:Alkaline Phosphatase