title: RANKL inhibits cell proliferation by regulating MALAT1 expression in a human osteoblastic cell line hFOB 1.19.
abstract: Receptor activator of NF&mdash;&#954;B ligand (RANKL), a TNF&mdash;related protein, is a key factor regulating bone metabolism. It has been well known that RANKL&mdash;mediated signaling regulates the formation, activation and survival of osteoclast in normal bone modeling and remodeling, and also plays an important role in a variety of pathologic conditions. However, there is no direct evidence about the effect of RANKL on osteoblast. Herein, we investigated whether RANKL had effect on cell proliferation in a normal human fetal osteoblastic cell line hFOB 1.19. MTT assay showed that RANKL inhibited hFOB 1.19 cells growth in a dose&mdash;dependent and time&mdash;dependent manner. Importantly, we found that RANKL induced the expression of a lncRNA, MALAT1, for the first time. Knockdown of RANK by siRNA blocked the induction of MALAT1 by RANKL. By infection with MALAT1 siRNA, MALAT1 knockdown reversed RANKL&mdash;induced cells growth inhibition and cell cycle arrest. In addition, MALAT1 also regulated OPG expression in hFOB 1.19 cells. In conclusion, RANKL, binding to its receptor RANK, inhibited cell proliferation via MALAT1 upregulation in osteoblast cells in vitro.
authors: Zhongshan Hospital, Fudan University Department of Orthopedics Surgery Shanghai China.
authors: W
authors: W
authors: Che
authors: Shanghai Medical College, Fudan University Department of Neurology and Institute of Neurology Shanghai China.
authors: Y
authors: Y
authors: Dong
authors: Zhongshan Hospital, Fudan University Department of Internal Medicine Shanghai China QUANHONGBO2004&commat;hotmail.com.
authors: H-B
authors: HB
authors: Quan
mesh_terms: D001842:Bone and Bones / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D066298:In Vitro Techniques; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C557041:MALAT1 long non-coding RNA, human; D053244:Osteoprotegerin; D053245:RANK Ligand; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C505688:TNFSF11 protein, human