title: Sphingomyelin Phosphodiesterase 3 Enhances Cytodifferentiation of Periodontal Ligament Cells.
abstract: Sphingomyelin phosphodiesterase 3 ( Smpd3), which encodes neutral sphingomyelinase 2 (nSMase2), is a key molecule for skeletal development as well as for the cytodifferentiation of odontoblasts and alveolar bone. However, the effects of nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still unclear. In this study, the authors analyzed the effects of Smpd3 on the cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3 increases the mRNA expression of calcification-related genes, such as alkaline phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation. Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3 in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated subjects, the authors identified a single nucleotide polymorphism (SNP), rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people. Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2, suggesting that this SNP inhibits Smpd3 such that it has no effect on the cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial role in maintaining the homeostasis of PDL tissue.
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miyauchi
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kitagaki
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Masumoto
authors.affiliation: 2 Department of Genome Informatics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Imai
authors.affiliation: 2 Department of Genome Informatics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|3 Medical Solutions Division, NEC Corporation, Minato-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: 2 Department of Genome Informatics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nakaya
authors.affiliation: 4 Challenge to Intractable Oral Disease, Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kawai
authors.affiliation: 5 Challenge to Intractable Oral Disease, Center for Translational Dental Research, Osaka University Dental Hospital, Suita, Osaka, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Fujihara
authors.affiliation: 6 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Asano
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yanagita
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: 1 Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000328:Adult; D010520:Aggressive Periodontitis / Q000201:enzymology / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D015151:Immunoblotting; D007564:Japan; D008297:Male; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000502:physiology*
chemical_list: D024042:Collagen Type I; C506895:SPP1 protein, human; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase; D013108:Sphingomyelin Phosphodiesterase
keywords: aggressive periodontitis; calcification; cell biology; genome-wide association study; molecular biology; single nucleotide polymorphism