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

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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-β (TGF-β) is thought to cause the pathogenesis for lung and cardiovascular abnormalities in MFS1. Interestingly, M-HPL1 shows a higher level of activated TGF-β 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.

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Acknowledgements

The authors thank Dr. K. Ohyama (former Professor of Tokyo Medical and Dental University), Dr. S. Yamada (Osaka University), and Professor S. Murakami (Osaka University) for their valuable advice and discussion. The authors are also grateful to Professor T. Yoda (Saitama Medical University) and Dr. Y. Fukushima (Saitama Medical University) for organizing the tooth samples and providing the medical history of the patient. The authors also express their gratitude to Marfan Network Japan (MNJ) for their cooperation in the present research. Additional thanks are extended to Dr. T. Yokoi (Aichi Gakuin University), Dr. T. Tsubakimoto (Kanagawa Dental College), Dr. E. Nishida (Aichi Gakuin University), Dr. K. Kosaka (Kanagawa Dental College), and Dr. M. Aino (Aichi Gakuin University) for their technical assistance.

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Authors and Affiliations

  1. Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Momotoshi Shiga, Mitsu Hattori & Naoto Suda

  2. Department of Molecular and Cellular Biochemistry, Graduate School of Dentistry, Osaka University, Osaka, 565-0871, Japan

    Masahiro Saito

  3. Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Chiharu Torii & Kenjiro Kosaki

  4. Virology Division, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

    Tohru Kiyono

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  1. Momotoshi Shiga
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  2. Masahiro Saito
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  3. Mitsu Hattori
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  4. Chiharu Torii
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  5. Kenjiro Kosaki
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  7. Naoto Suda
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Correspondence to Naoto Suda.

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This work was supported by Grants-in-Aid (16390604, 16659570, and 18390552) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Shiga, M., Saito, M., Hattori, M. et al. Characteristic phenotype of immortalized periodontal cells isolated from a Marfan syndrome type I patient. Cell Tissue Res 331, 461–472 (2008). https://doi.org/10.1007/s00441-007-0528-x

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