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.
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.
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