New cementum formation induced by cyclosporin A: a histological, ultrastructural and histomorphometric study in the rat

Abstract

Cyclosporin A (CsA), a widely used immunosuppressive agent, is known to induce gingival overgrowth; 30 mg/kg/d of CsA were administrated orally in young and adult male Sprague-Dawley rats. The same number of rats received oil-based vehicle solution. After 4, 9, 14 and 19 wk of CsA or vehicle administration 3 control and 3 experimental rats were anaesthetized and tissues fixed by an intracardiac perfusion of fixative solution. Upper and lower jaws were dissected, demineralized and processed for Epon inclusion. Histological examination revealed the presence of large amounts of new cementum (NC) covering extensive areas of the acellular extrinsic fibre cementum (AEFC) in all the root surfaces. NC was particularly abundant at the cervical third of the roots facing the gingival connective tissue, where it occurred as layers, spurs or in both configurations. NC was characterized by its irregular outline, globular body content and infrequent presence of incremental lines. Histomorphometric evaluation by semi-automatic image analysis indicated that the volume and the external surface of NC spurs were 2.86-6.49 and 1.29-1.97-fold increased comparative to those of the AEFC covering the same root areas. Electron microscopy revealed that NC was a functional tissue with insertion of collagen fibres perpendicularly to the long axis of the root. It can be concluded that under some experimental conditions formation of abundant amounts of NC can be achieved and that these results must be taken into account for a new approach in the treatment of periodontal disease.

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

“…These formations show different histological characteristics than those of the structures found in normal GCT (4), while ectopic calcifications have been observed in gingiva of patients with dental or periodontal disorders ( 5 ) . The NCLIs show a structure and structural variations identical to the adjacent NC and exhibit its 2 main structural characteristics, incremental lines and globular bodies (1). The administration of a particular dose of CsA during a specific duration seems to be related to the formation of these structures.…”

“…This investigation was performed in 6-wk-old male Sprague-Dawley rats; 3 control and 3 experimental rats received oil-based vehicle and CsA solutions, respectively (kindly supplied by Sandoz, Rueil-Malmaison, France) in a daily dose of 30 mg/kg of body weight by gavage for 14 wk. The methods employed for the standard preparation of the tissues for Epon inclusion have been described recently (1). The procedure involved fixation (by perfusion and immersion) with aldehydes, demineralization in EDTA, hemisection of jaws in buccal and lingual halves, post-fixation in OsO,, dehydratation and embedding in Epon 812.…”

“…During the examination of histological sections of the periodontal tissues in cyclosporin A (CsA)treated rats (1) we observed the presence of unknown formations located inside the gingival connective tissue (GCT) close to the root surface but without any obvious contact with it. In an attempt to characterize these formations several areas were cut by serial sectioning.…”

Cyclosporin a-induced new cementum formation: a morphometric evaluation in the periapical region of rats

“…Its occurrence did not vary between rats of the same group. The (11)(12)(13) suggested that the occurrence and volume of cementum overgrowth are independent on the root surface, molar teeth or age of rats and, dependent partly on the administration time. The present study was designed to evaluate the thickness of cementum and volume density of cementoblasts during and after CsA treatment.…”

“…It is well established that CsA causes gingival overgrowth, bone loss and induces cementum deposition (7)(8)(9)(10)(11)(12)(13)(14). It has been shown that CsA administrated orally to rats induces abundant new cementum formation with functionally inserting collagen fibers (12,13). New cementum is deposited on the afibrillar extrinsic fiber cementum, mainly on the cervical third of the roots, as irregular layers, spurs of various sizes and shapes, or in both configurations.…”