PMID- 24117017 OWN - NLM STAT- MEDLINE DCOM- 20140831 LR - 20211021 IS - 1937-335X (Electronic) IS - 1937-3341 (Print) IS - 1937-3341 (Linking) VI - 20 IP - 1-2 DP - 2014 Jan TI - Hypoxia promotes CEMP1 expression and induces cementoblastic differentiation of human dental stem cells in an HIF-1-dependent manner. PG - 410-23 LID - 10.1089/ten.TEA.2013.0132 [doi] AB - Cementum covering the tooth root provides attachment for the tooth proper to the surrounding alveolar bone via non-mineralized periodontal ligament (PDL). Cementum protein 1 (CEMP1) has been shown to induce a cementoblastic phenotype in cementoblast precursors cells of PDL. Oxygen availability is a critical signal for correct development of many tissues; however, its role in tooth root and periodontium development remains poorly understood. In this study, we demonstrated that reduced oxygen tension increased CEMP1 expression, mineral deposition, and alkaline phosphatase activity in human dental stem cells such as PDL stem cells and periapical follicular stem cells. Since an oxemic state is transduced by the transcription factor, hypoxia-inducible factor-1 (HIF-1), we performed experiments to determine whether this protein was responsible for the observed changes. We noted that when HIF-1 was activated by gene introduction or chemically, CEMP1 expression and mineralization increased. In contrast, when HIF-1alpha was silenced, CEMP1 expression and mineralization did not increase in vitro. Furthermore, we showed for the first time that mouse tooth root and periodontium development occurs partly under hypoxic conditions, particularly at the apical part and latently at the PDL space in vivo. Desferrioxamine, an HIF-1 stimulator, enhances CEMP1 expression in the mouse PDL space, suggesting that hypoxia affects cementogenesis of PDL cells lining the surface of the developing tooth root in an HIF-1-dependent manner. These results suggest that HIF-1 activators may have the ability to stimulate regeneration of the tooth root and cementum formation. FAU - Choi, Hwajung AU - Choi H AD - 1 Department of Oral and Maxillofacial Surgery, Dental Research Institute, School of Dentistry, Seoul National University , Seoul, Korea. FAU - Jin, Hexiu AU - Jin H FAU - Kim, Jin-Young AU - Kim JY FAU - Lim, Ki-Taek AU - Lim KT FAU - Choung, Han-Wool AU - Choung HW FAU - Park, Joo-Young AU - Park JY FAU - Chung, Jong Hoon AU - Chung JH FAU - Choung, Pill-Hoon AU - Choung PH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (CEMP1 protein, human) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Proteins) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - S88TT14065 (Oxygen) SB - IM MH - Adolescent MH - Adult MH - Alkaline Phosphatase/metabolism MH - Animals MH - Calcification, Physiologic/drug effects MH - *Cell Differentiation/drug effects MH - Cell Hypoxia/drug effects MH - Cell Proliferation/drug effects MH - Cementogenesis/drug effects MH - Dental Cementum/*cytology/drug effects/metabolism MH - Flow Cytometry MH - Humans MH - Hypoxia-Inducible Factor 1/*metabolism MH - Mice MH - Multipotent Stem Cells/cytology/drug effects/metabolism MH - Oxygen/pharmacology MH - Periodontal Ligament/cytology MH - Protein Stability/drug effects MH - Proteins/*metabolism MH - RNA Interference MH - Signal Transduction/drug effects MH - Stem Cells/*cytology/drug effects/enzymology MH - Tooth Root/cytology MH - Young Adult PMC - PMC3875148 EDAT- 2013/10/15 06:00 MHDA- 2014/09/01 06:00 PMCR- 2015/01/01 CRDT- 2013/10/15 06:00 PHST- 2013/10/15 06:00 [entrez] PHST- 2013/10/15 06:00 [pubmed] PHST- 2014/09/01 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.1089/ten.tea.2013.0132 [pii] AID - 10.1089/ten.TEA.2013.0132 [doi] PST - ppublish SO - Tissue Eng Part A. 2014 Jan;20(1-2):410-23. doi: 10.1089/ten.TEA.2013.0132.