PMID- 37099814 OWN - NLM STAT- MEDLINE DCOM- 20230508 LR - 20230512 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 662 DP - 2023 Jun 25 TI - Lysosomal acid lipase regulates bioenergetic process during the cytodifferentiation of human periodontal ligament cells. PG - 84-92 LID - S0006-291X(23)00450-3 [pii] LID - 10.1016/j.bbrc.2023.04.041 [doi] AB - Lipid metabolism is one of energy metabolic pathways that produce adenosine triphosphate (ATP). In this pathway, lysosomal acid lipase (LAL) encoded by Lipase A (LIPA), plays an important role in catalyzing lipids to fatty acids (FAs), which drive oxidative phosphorylation (OXPHOS) and generate ATP. Previously, we found that a LIPA single nucleotide polymorphism rs143793106, which decreases the LAL activity, suppressed the cytodifferentiation of human periodontal ligament (HPDL) cells. However, the mechanisms underlying that suppression are still not fully clarified. Thus, we aimed to investigate the mechanisms regulating the cytodifferentiation of HPDL cells by LAL in terms of energy metabolism. We performed the osteogenic induction of HPDL cells with or without Lalistat-2, a LAL inhibitor. To visualize lipid droplet (LD) utilization, we performed confocal microscopy on HPDL cells. We also performed real-time PCR to analyze the gene expression of calcification-related and metabolism-related genes. Furthermore, we measured the ATP production rate from two major energy production pathways, OXPHOS and glycolysis, and OXPHOS-related parameters of HPDL cells during their cytodifferentiation. We found that LDs were utilized during the cytodifferentiation of HPDL cells. Alkaline phosphatase (ALPL), collagen type 1 alpha 1 chain (COL1A1), ATP synthase F1 subunit alpha (ATP5F1A), and carnitine palmitoyltransferase 1A (CPT1A) mRNA expressions were upregulated, whereas lactate dehydrogenase A (LDHA) mRNA expression was downregulated. Additionally, total ATP production rate was significantly increased. In contrast, in the presence of Lalistat-2, LD utilization was inhibited and ALPL, COL1A1, and ATP5F1A mRNA expression was downregulated. Additionally, ATP production rate and spare respiratory capacity of the OXPHOS pathway were decreased in HPDL cells during their cytodifferentiation. Collectively, the defect of LAL in HPDL cells decreased LD utilization and OXPHOS capacity, resulting in reduced energy to sustain the adequate ATP production required for the cytodifferentiation of HPDL cells. Thus, LAL is important for periodontal tissue homeostasis as a regulator of bioenergetic process of HPDL cells. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Nantakeeratipat, Teerachate AU - Nantakeeratipat T AD - Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Conservative Dentistry and Prosthodontics, Faculty of Dentistry, Srinakharinwirot University, 114 Soi Sukhumvit 23, Khlong Toei Nuea, Watthana, Bangkok, 10110, Thailand. Electronic address: teerachate@g.swu.ac.th. FAU - Fujihara, Chiharu AU - Fujihara C AD - Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: fujihara.chiharu.dent@osaka-u.ac.jp. FAU - Nogimori, Takuto AU - Nogimori T AD - Laboratory of Immunosenescence, Center for Vaccine & Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan. Electronic address: tnogimori@nibiohn.go.jp. FAU - Matsumoto, Masahiro AU - Matsumoto M AD - Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: matsumoto.masahiro.dent@osaka-u.ac.jp. FAU - Yamamoto, Takuya AU - Yamamoto T AD - Laboratory of Immunosenescence, Center for Vaccine & Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan. Electronic address: yamamotot2@nibiohn.go.jp. FAU - Murakami, Shinya AU - Murakami S AD - Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: murakami.shinya.dent@osaka-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230417 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - EC 3.1.1.13 (Sterol Esterase) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - *Sterol Esterase MH - *Periodontal Ligament MH - Oxidative Phosphorylation MH - Adenosine Triphosphate MH - RNA, Messenger MH - Cells, Cultured OTO - NOTNLM OT - Adenosine triphosphate OT - Energy metabolism OT - Lysosomal acid lipase OT - Mineralized tissue OT - Periodontal ligament COIS- Declaration of interest statement The authors declare that they have no conflict of interest. EDAT- 2023/04/26 18:42 MHDA- 2023/05/08 06:42 CRDT- 2023/04/26 18:00 PHST- 2023/04/08 00:00 [received] PHST- 2023/04/15 00:00 [accepted] PHST- 2023/05/08 06:42 [medline] PHST- 2023/04/26 18:42 [pubmed] PHST- 2023/04/26 18:00 [entrez] AID - S0006-291X(23)00450-3 [pii] AID - 10.1016/j.bbrc.2023.04.041 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2023 Jun 25;662:84-92. doi: 10.1016/j.bbrc.2023.04.041. Epub 2023 Apr 17.