CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
FEBS Lett. 2013 Sep 17;587(18):2958-64. doi: 10.1016/j.febslet.2013.08.005. Epub 2013 Aug 13.
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.
肠肽酶可以在 Asp-Asp-Asp-Asp-Lys 序列上切割胰蛋白酶原，在食物消化中发挥重要作用。RANKL-RANK 信号通路在骨重塑中起着关键作用。在这项研究中，我们报告肠肽酶可以通过切割 RANK 来抑制 RANKL-RANK 信号通路。替代肽阻断试验表明，肠肽酶可以在 NEEDK 序列上特异性切割 RANK。破骨细胞分化试验和 NF-κB 活性试验证实，肠肽酶可以通过切割 RANK 抑制体外破骨细胞生成。这是第一项证明 RANKL-RANK 信号通路可以通过切割 RANK 而不是针对 RANKL 来抑制的研究。
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