Cyclosporin A‐induced alterations of dentinogenesis in rat molars

Abstract

Cyclosporin A (CsA), a widely used immunosuppressive drug, induces gingival overgrowth and modifications of bone remodelling. The scope of this study was to investigate the possible effect of CsA on dentin. Thirty mg/kg/day of CsA were administered orally to male Sprague-Dawley rats for nineteen weeks. The same number of control rats received oil-based vehicle solution. Rats were anesthetized, and tissues were fixed by an intracardiac perfusion of fixative solution. Mandibles were dissected, demineralized, and processed for Epon embedding. Semi-thin sections of the first molars revealed alterations at the secondary dentin-pulp interface in four out of six experimental animals. The changes consisted of the formation of: 1) osteodentin spurs, in which the volume and interface with the secondary dentin varied from about 25,000 to 75,000 microns 3 and from 1400 to 3530 microns 2, respectively; 2) abnormally shaped and irregularly spaced incremental lines; and 3) numerous globular formations embedded in dentin or free in the pulp. These results indicate that CsA induces abnormal mineralized matrix formation in dentin and in the peripheral part of the pulp in rat molars.

Cyclosporin A promotes mineralization by human cementoblastoma‐derived cells in culture

“…This could be a result of different cell subpopulations responding differently to the drug and clonal selection promoted by cyclosporin A. This possibility is supported by the observations that cyclosporin A induced phenotypic modifications in gingival fibroblasts that resulted in differentiation of cementoblast‐like cells (13), and in the formation of osteodentin spurs deposited on dentin (29). We believe that cyclosporin A induced suppression of proliferation of cementoblastoma cells, but not gingival fibroblasts, due to its promoting differentiation and mineral nodule formation by the cementoblastoma cells.…”

“…The study by Ayanoglou et al . (13) revealed that cyclosporin A promotes osteodentin formation in rat molars and that it might increase the activity of odontoblasts by modifying its phenotype or by increasing the number of cells, or by both mechanisms. Ayanoglou (14) also found that oral administration of cyclosporin A in Sprague‐Dawley rats promoted the formation of mineralized islets inside the gingival connective tissue in the proximity of root surfaces and voluminous deposits of new cementum covering the root areas, and postulated that cyclosporin A stimulates paravascular cementoblast progenitor cells.…”

Dental and Craniofacial Effects on Childhood Cancer Survivors

“…Ayanoglou et al examined the effect of cyclosporine A (CsA) in rats' molars. The reduction in dentin matrix mineralization and time prolongation was observed in the process, and as a consequence of this, lesions similar to dentinogenesis imperfecta starts in the dentin [57,113].…”

Evidence that cyclosporin A administration induces the formation of new cementum‐like islets inside the gingival connective tissue

“…in a continuous process of spherical structure elaboration, could not have been trapped inside their own product. Serial sectioning, however, did not reveal inside the NCLIs the presence of structures showing the typical histological appearance of cells, as was the case in the CsA-induced osteodentin formation (6). Therefore, trapped cells (adjacent to and/or secreting) may have undergone radical degenerative transformations and appear in sections in an altered form.…”

“…However, their systematic observation inside the 6. The NCLI-a shows structural variations: it is composed of a peripheral compact ring around a central less consolidate area (4), exhibits secondary compact capsules surrounding cell-like inclusions ( 5 ) , or shows a more condensed structure with incremental lines and globular bodies (6). V: blood vessel.…”