Marfan syndrome and its disorder in periodontal tissues

Abstract

Elastic system fibers are composed of two distinct elements, elastin, which is an amorphous component crosslinked in the core, and microfibril, localized in the periphery of elastin. As microfibrillar proteins, fibrillins, microfibril-associated glycoproteins (MAGPs), latent TGF-beta-binding proteins (LTBPs), microfibril-associated proteins (MFAPs), and fibulins are known. Fibrillin-1 is a major microfibrillar protein and characterized by calcium binding EGF-like (cbEGF) domain. Association between fibrillin-1 and TGF-beta is a recent topic of this field and this interaction is known to inactivate and target TGF-beta action. FBN1 encoding fibrillin-1 is a responsible gene for Marfan syndrome type 1 (MIM #154700), characterized by increased height and long limbs, ectopia lentis, and cardiovascular disorders, such as mitral valve prolapse and aortic dilation and regurgitation. Animal models suggest that the abnormal TGF-beta signaling is underlying as the pathogenesis of these conditions. Besides skeletal, ocular and cardiovascular conditions, severe periodontitis is frequently seen in affected patients. To clarify the unknown function of elastic system fibers in the periodontal ligament (PDL), PDL-cells were isolated from a Marfan syndrome type 1 patient who was with the severe periodontitis and had a mutation in one of the cbEGF domain of fibrillin-1. These results suggested that wild-type fibrillin-1 was required for the normal cell alignment and tissue architecture of PDLs. Evidences are now accumulated to suggest that fibrillin-1 is one of the molecule involved in the interaction between cell and extracellular matrix.

Effects of Fibrillin Application on Periodontal Ligament Regeneration in Mouse Model of Tooth Replantation

“…Interestingly, the fibers were mostly connected between the root and alveolar bone in a direction perpendicular to the tooth root axis. It has been reported that periostin expression in PDL is significantly decreased in fibrillindeficient mice, which exhibit loose connective tissue in the PDL 19,20) . In the present study, periostin was highly expressed in the PDL regenerated following application of 1 mg/ml fibrillin/ PGA.…”

“…We have previously shown that fibrillin 1 and 2 are initially expressed at the surface of the developing root and widely observed in mature human PDL tissue 17) . Furthermore, a mutation in the Fibrillin-1 gene causes Marfan syndrome, which displays orofacial manifestations and increases susceptibility to periodontal disease 18,19) . It has also been shown that fibrillin plays an important role in maintaining the PDL through interactions with periostin and collagen 20) model, and evaluated the regenerated PDL by fibrillin application, histochemicaly.…”

Advances in the Use of Growth Factors for Treatment of Disorders of Soft Tissues

“…PDGF alone, in particular the homodimer PDGF-BB, or in combination with IGF-I stimulated regeneration of periodontal ligament and its attachment to the alveolar bone [ 126 ], a matter of importance in Marfan patients with periodontitis. By the way, FGF2, discussed in more detail above, had similar effect on cells of the periodontal ligament [ 6 ]. PDGF was shown to improve healing and biomechanical parameters of acute injury of the medial collateral ligament in rabbits and rats, especially, if administered shortly after injury.…”

“…Surgical repair is usually incomplete as well, resulting in decreased stiffness and adhesion formation [ 4 , 5 ]. Patients with Marfan syndrome also suffer from joint problems and from periondontitis, or infl ammation of the gingiva, periodontal ligament and alveolar bone loss which does not accompany dental caries [ 6 ]. Though less obvious than in other tissues, healing of tendons and ligaments occurs through two pathways.…”

“…6 Though the authors concentrate on the cardiovascular system, TGFβ1 exerts similar effects on other soft tissue structures, such as bones and ligament as the two systems (cardiovascular and musculoskeletal) share certain developmental and regulatory mechanisms, and very similar extracellular matrix structure and composition [ 30 ]. However, it has been shown that TGFβ1 null mice suffer primarily from overwhelming infl ammatory processes and from vasculogenesis defects rather than from musculoskeletal problems, and that they die early in life [ 31 , 32 ].…”