ワタナベ ケイスケ
  渡辺 啓介
   所属   新潟薬科大学  医療技術学部 臨床検査学科
   職種   教授
言語種別 英語
発行・発表の年月 2023
形態種別 論文
査読 査読あり
標題 Inductive effect of SORT1 on odontoblastic differentiation of human dental pulp-derived stem cells.
執筆形態 共著
掲載誌名 Differentiation; research in biological diversity
掲載区分国外
巻・号・頁 133,pp.88-97
著者・共著者 Daisuke Omagari,Taku Toriumi,Hiromasa Tsuda,Manabu Hayatsu,Keisuke Watanabe,Yusuke Mizutami,Masaki Honda,Yoshikazu Mikami
概要 This study investigated the expression of sortilin 1 (SORT1) in cultured human dental pulp-derived stem cells (hDPSCs) and its role in their odontoblastic differentiation. Permanent teeth were extracted from five patients, and the dental pulp was harvested for explant culture. Fluorescence-activated cell sorting was used to analyze the outgrowth of adherent cells and cells that had migrated from the tissue margin. SORT1 expression was detected in hDPSCs simultaneously expressing the mesenchymal stem cell markers CD44 and CD90. The odontoblastic differentiation potential of SORT1-positive hDPSCs was examined via staining for alkaline phosphatase (ALP), an early odontoblastic differentiation marker. ALP staining was more intense in SORT1-positive than in SORT1-negative hDPSCs. Consistently, the expression of mRNA encoding SORT1 and p75NTR, a binding partner of SORT1, increased in SORT1-positive hDPSCs during odontoblastic differentiation. In addition, pro-nerve growth factor (NGF), a ligand for SORT1-p75NTR co-receptor, promoted ALP expression in SORT1-positive hDPSCs, and the interaction between SORT1 and p75NTR was detected using a coimmunoprecipitation assay. The function of SORT1 in odontoblastic differentiation was examined via RNA interference using shRNA targeting SORT1. ALP staining intensity in SORT1/shRNA-transfected cells was markedly lower than in control/shRNA-transfected cells. SORT1 knockdown decreased JUN phosphorylation and recruitment of phosphorylated JUN to the ALP promoter. Collectively, these results indicate that SORT1 is involved in the odontoblastic differentiation of hDPSCs through the JUN N-terminal kinases (JNK)/JUN signaling pathway and that the binding of SORT1 and p75NTR plays an important role in this process.
DOI 10.1016/j.diff.2023.08.001
PMID 37579565