{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:52:46Z","timestamp":1780483966536,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Aggressive periodontitis (AgP) is characterized by general health and rapid destruction of periodontal tissue. The familial aggregation of this disease highlights the involvement of genetic factors in its pathogeny. We conducted a genome\u2010wide association study (GWAS) to identify AgP\u2010related genes in a Japanese population, and the lipid metabolism\u2010related gene, lipase\u2010a, lysosomal acid type (<jats:italic>LIPA<\/jats:italic>), was suggested as an AgP candidate gene. However, there is no report about the expression and function(s) of <jats:italic>LIPA<\/jats:italic> in periodontal tissue. Hence, we studied the involvement of how <jats:italic>LIPA<\/jats:italic> and its single\u2010nucleotide polymorphism (SNP) rs143793106 in AgP by functional analyses of <jats:italic>LIPA<\/jats:italic> and its SNP in human periodontal ligament (HPDL) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>GWAS was performed using the genome database of Japanese AgP patients, and the GWAS result was confirmed using Sanger sequencing. We examined the mRNA expression level of <jats:italic>LIPA<\/jats:italic> and the protein expression level of the encoded protein lysosomal acid lipase (LAL) in periodontium\u2010composing cells using conventional and real\u2010time polymerase chain reaction (PCR) and western blotting, respectively. Lentiviral vectors expressing <jats:italic>LIPA<\/jats:italic> wild\u2010type (<jats:italic>LIPA<\/jats:italic> WT) and <jats:italic>LIPA<\/jats:italic> SNP rs143793106 (<jats:italic>LIPA<\/jats:italic> mut) were transfected into HPDL cells. Western blotting was performed to confirm the transfection. LAL activity of transfected HPDL cells was determined using the lysosomal acid lipase activity assay. Transfected HPDL cells were cultured in mineralization medium. During the cytodifferentiation of transfected HPDL cells, mRNA expression of calcification\u2010related genes, alkaline phosphatase (ALPase) activity and calcified nodule formation were assessed using real\u2010time PCR, ALPase assay, and alizarin red staining, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The GWAS study identified 11 AgP\u2010related candidate genes, including <jats:italic>LIPA<\/jats:italic> SNP rs143793106. The minor allele frequency of <jats:italic>LIPA<\/jats:italic> SNP rs143793106 in AgP patients was higher than that in healthy subjects. <jats:italic>LIPA<\/jats:italic> mRNA and LAL protein were expressed in HPDL cells; furthermore, they upregulated the cytodifferentiation of HPDL cells. LAL activity was lower in <jats:italic>LIPA<\/jats:italic> SNP\u2010transfected HPDL cells during cytodifferentiation than that in <jats:italic>LIPA<\/jats:italic> WT\u2010transfected HPDL cells. In addition, ALPase activity, calcified nodule formation, and calcification\u2010related gene expression levels were lower during cytodifferentiation in <jats:italic>LIPA<\/jats:italic> SNP\u2010transfected HPDL cells than those in <jats:italic>LIPA<\/jats:italic> WT\u2010transfected HPDL cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>LIPA<\/jats:italic>, identified as an AgP\u2010related gene in a Japanese population, is expressed in HPDL cells and is involved in regulating cytodifferentiation of HPDL cells. <jats:italic>LIPA<\/jats:italic> SNP rs143793106 suppressed cytodifferentiation of HPDL cells by decreasing LAL activity, thereby contributing to the development of AgP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13079","type":"journal-article","created":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T05:58:44Z","timestamp":1670651924000},"page":"175-183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lipase\u2010a single\u2010nucleotide polymorphism rs143793106 is associated with increased risk of aggressive periodontitis by negative influence on the cytodifferentiation of human periodontal ligament cells"],"prefix":"10.1111","volume":"58","author":[{"given":"Masahiro","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Periodontology Osaka University Graduate School of Dentistry  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Department of Periodontology Osaka University Graduate School of Dentistry  Osaka 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