title: Inhibition effect of enteropeptidase on RANKL-RANK signalling by cleavage of RANK.
abstract: Enteropeptidase can cleave trypsinogen on the sequence of Asp-Asp-Asp-Asp-Lys and plays an important role in food digestion. The RANKL-RANK signalling pathway plays a pivotal role in bone remodelling. In this study, we reported that enteropeptidase can inhibit the RANKL-RANK signalling pathway through the cleavage of RANK. A surrogate peptide blocking assay indicated that enteropeptidase could specifically cleave RANK on the sequence NEEDK. Osteoclast differentiation assay and NF-κB activity assay confirmed that enteropeptidase could inhibit osteoclastogenesis in vitro through the cleavage of RANK. This is the first study to prove that the RANKL-RANK signalling pathway can be inhibited by cleavage of RANK instead of targeting RANKL.
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. brookyzhao@yahoo.com
authors: Yunfeng
authors: Y
authors: Zhao
authors: Mengmeng
authors: M
authors: Jin
authors: Juan
authors: J
authors: Ma
authors: Shiqian
authors: S
authors: Zhang
authors: Wei
authors: W
authors: Li
authors: Yuan
authors: Y
authors: Chen
authors: Yingsheng
authors: Y
authors: Zhou
authors: Hong
authors: H
authors: Tao
authors: Yu
authors: Y
authors: Liu
authors: Lei
authors: L
authors: Wang
authors: Huamin
authors: H
authors: Han
authors: Ge
authors: G
authors: Niu
authors: Hua
authors: H
authors: Tao
authors: Changzhen
authors: C
authors: Liu
authors: Bin
authors: B
authors: Gao
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002454:Cell Differentiation; D002460:Cell Line; D004765:Enteropeptidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D004765:Enteropeptidase
keywords: BMM; EP; Enteropeptidase/EP; M-CSF; Osteoclastogenesis; RANK; RANKL; RANKL–RANK signalling pathway; TNFRSF18; TRAP; bone marrow-derived macrophage; enteropeptidase; macrophage-colony stimulating factor; receptor of activator of NF-κB; receptor of activator of NF-κB ligand; tartrate-resistant acid phosphatase; tumour necrosis factor receptor superfamily 18