title: Negative effects of retinoic acid on stem cell niche of mouse incisor.
abstract: The continuous growth of mouse incisors depends on epithelial stem cells (SCs) residing in the SC niche, called labial cervical loop (LaCL). The homeostasis of the SCs is subtly regulated by complex signaling networks. In this study, we focus on retinoic acid (RA), a derivative of Vitamin A and a known pivotal signaling molecule in controlling the functions of stem cells (SCs). We analyzed the expression profiles of several key molecules of the RA signaling pathway in cultured incisor explants upon exogenous RA treatment. The expression patterns of these molecules suggested a negative feedback regulation of RA signaling in the developing incisor. We demonstrated that exogenous RA had negative effects on incisor SCs and that this was accompanied by downregulation of Fgf10, a mesenchymally expressed SC survival factor in the mouse incisor. Supplement of Fgf10 in incisor cultures completely blocked RA effects by antagonizing apoptosis and increasing proliferation in LaCL epithelial SCs. In addition, Fgf10 obviously antagonized RA-induced downregulation of the SC marker Sox2 in incisor epithelial SCs. Our findings suggest that the negative effects of RA on incisor SCs result from inhibition of mesenchymal Fgf10.
authors: Department of Pharmacy, Wuhan University of Science and Technology School of Medicine, 2 West Huangjiahu Road, Wuhan, Hubei 430065, China.
authors: Jinlei
authors: J
authors: Xi
authors: Department of Pharmacology, Wuhan University School of Basic Medical Science, 185 Donghu Road, Wuhan, Hubei 430071, China.
authors: Shijing
authors: S
authors: He
authors: Department of Pharmacology, Wuhan University School of Basic Medical Science, 185 Donghu Road, Wuhan, Hubei 430071, China.
authors: Cizhao
authors: C
authors: Wei
authors: Department of Pharmacology, Wuhan University School of Basic Medical Science, 185 Donghu Road, Wuhan, Hubei 430071, China.
authors: Wanyao
authors: W
authors: Shen
authors: Department of Pharmacy, Wuhan University of Science and Technology School of Medicine, 2 West Huangjiahu Road, Wuhan, Hubei 430065, China.
authors: Juan
authors: J
authors: Liu
authors: Department of Pharmacology, Wuhan University School of Basic Medical Science, 185 Donghu Road, Wuhan, Hubei 430071, China.
authors: Ke
authors: K
authors: Li
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
authors: Yufeng
authors: Y
authors: Zhang
authors: Department of Pharmacology, Wuhan University School of Basic Medical Science, 185 Donghu Road, Wuhan, Hubei 430071, China.
authors: Jiang
authors: J
authors: Yue
authors: Department of Pharmacology, Wuhan University School of Basic Medical Science, 185 Donghu Road, Wuhan, Hubei 430071, China. Electronic address: zheqiong_yang@whu.edu.cn.
authors: Zheqiong
authors: Z
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051526:Fibroblast Growth Factor 10 / Q000096:biosynthesis; D007180:Incisor / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000187:drug effects*; D014212:Tretinoin / Q000633:toxicity*
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D014212:Tretinoin
keywords: Apoptosis; Fgf10; Proliferation; Retinoic acid; Stem cell; Tooth