Characteristic phenotype of immortalized periodontal cells isolated from a Marfan syndrome type I patient

Abstract

The periodontal ligament (PDL) is situated between the tooth root and alveolar bone, thereby supporting the tooth, and is composed of collagen and elastic system fibers. Marfan syndrome type I (MFS1, MIM #154700) is caused by mutations in FBN1 encoding fibrillin-1, which is a major microfibrillar protein of elastic system fibers. MFS1 is characterized by tall stature, aortic/mitral valve prolapse, and ectopia lentis and is occasionally accompanied by severe periodontitis. Since little is known about the biological functions of elastic system fibers in PDLs and the pathogenesis of the periodontitis in MFS1, PDL cells were isolated from an MFS1 patient with a heterozygous missense mutation in a calcium-binding epidermal-growth-factor-like domain of FBN1. Isolated PDL cells were immortalized by transducing a retrovirus carrying genes for the human Polycomb group protein, Bmi-1, and human telomerase reverse transcriptase. Immortalized PDL cells from the MFS1 patient (termed M-HPL1) and those of a healthy volunteer (termed HPDL2) both expressed various PDL-related genes. The growth and attachment of M-HPL1 and HPDL2 to hydroxyapatite particles were comparable. However, when M-HPL1 were transplanted with hydroxyapatite particles into immunodeficient mice, disorganized cell alignment and irregular microfibril assembly were noted. The activation of the signaling of transforming grwoth factor-beta (TGF-beta) is thought to cause the pathogenesis for lung and cardiovascular abnormalities in MFS1. Interestingly, M-HPL1 shows a higher level of activated TGF-beta than HPDL2. Thus, M-HPL1 represent a powerful tool for clarifying the biological roles of elastic system fibers in PDL and the pathogenesis of periodontitis in MFS1. Our findings also suggest that FBN1 regulates cell alignment and microfibril assembly in PDLs.

ADAMTSL6β Protein Rescues Fibrillin-1 Microfibril Disorder in a Marfan Syndrome Mouse Model through the Promotion of Fibrillin-1 Assembly

“…Tissue Culture and in Vitro Microfibril Assembly Assay-The establishment of immortalized human periodontal cells and MHPDL cells has been described previously (25). Cells were incubated with ␣-minimum essential medium (Sigma) containing 10% fetal bovine serum (FBS; BioWhittaker, Walkersville, MD), 50 g/ml ascorbic acid, and 100 units/ml streptomycin and penicillin in a humidified atmosphere of 5% CO 2 at 37°C.…”

“…5C). We next investigated the effects of ADAMTSL6␤ on human PDL cells obtained from an MFS patient with severe periodontitis (MHPDL) (25). As expected, ADAMTSL6␤ overexpression in these MHPDL cells clearly reduced periostin expression when compared with mock-infected cells.…”

Trends in Periodontal Regeneration Therapy: Potential Therapeutic Strategy of Extracellular Matrix Administration for Periodontal Ligament Regeneration

“…Among the ECM formations in the PDL, fibrillin-1, a major component of the microfibrils that regulate tissue integrity and elasticity, has been shown to contribute to the formation and maintenance of PDL [31]. Various mouse models of Marfan's syndrome (MFS) have been established via gene targeting or missense mutations, with germline mutations in fibrillin-1 leading to progressive connective tissue destruction due to fibrillin-1 fragmentation in association with an insufficiency of fibrillin-1 microfibril formation [32][33][34][35].…”

Syndrome de Marfan et chirurgie implantaire

“…Des études in vitro et in vivo ont montré la pré-sence d'altération structurale des tissus parodontaux lors qu'il y a une altération de la fibrilline type I. Ces altérations, aggravées par la plaque et la mauvaise hygiène bucco-dentaire, aboutissent à des parodontites agressive ou chronique [9,10,11] . Ceci constitue une contre-indication relative à la pose d'implant [7] .…”