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

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.