title: Effects of sodium tri- and hexameta-phosphate in vitro osteoblastic differentiation in Periodontal Ligament and Osteoblasts, and in vivo bone regeneration.
abstract: The present study was designed to assess the effects and underlying mechanism of two poly(P) compounds, sodium triphosphate (STP, Na5P3O10) and sodium hexametaphosphate (SHMP, Na15P13O40~Na20P18O40) on osteoblastic differentiation of human periodontal ligament cells (PDLCs) and osteoblasts in vitro, and bone formation in vivo. Differentiation was assessed by alkaline phosphatase (ALP) activity, mineralization, and mRNA expression for marker genes. To examine the osteogenic potential to regenerate bone, the critical-sized mouse calvarial defect model was utilized. Incubation of PDLCs and osteoblasts with STP and SHMP resulted in a dose- and time-dependent increase in growth, alkaline phosphatase (ALP) activity, mineralization and mRNA expression for marker genes. STP and SHMP increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), Akt, and mammalian target of rapamycin (mTOR), and mitogen-activated protein kinases (MAPK). Treatment with the mTOR inhibitor, rapamycin, attenuatted STP- and SHMP-induced osteoblastic differentiation. Micro-CT and histologic analysis showed that STP significantly increased new bone formation in calvarial defects, compared with SHMP and control group. Collectively, this is the first study to demonstrate that STP and SHMP promotes the osteoblastic differentiation in vitro, whereas STP only stimulated bone repair in vivo. Therefore, STP may be useful therapeutic approach for the regeneration of bone or periodontal tissue.
authors.affiliation: Department of Oral and Maxillofacial Pathology, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Bae
authors.affiliation: Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Q-Schick
authors.initials: QS
authors.lastname: Auh
authors.affiliation: Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Gyu-Tae
authors.initials: GT
authors.lastname: Kim
authors.affiliation: Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ji-Hoi
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Department of Oral and Maxillofacial Pathology, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address: eckim@khu.ac.kr.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010513:Periodontal Ligament / Q000187:drug effects / Q000254:growth & development*; D010710:Phosphates / Q000008:administration & dosage; D011122:Polyphosphates / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D020123:Sirolimus / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D010710:Phosphates; D011122:Polyphosphates; D012333:RNA, Messenger; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C005692:triphosphoric acid; C009285:sodium polymetaphosphate; D020123:Sirolimus
keywords: Differentiation; Growth; Osteoblast; Sodium hexametaphosphate; Sodium triphosphate; mTOR