DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
DEL-1 (developmental endothelial locus-1) is an endothelial cell-secreted protein that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin-dependent leukocyte recruitment and inflammation in various tissues. We identified a novel regulatory mechanism of DEL-1 in osteoclast biology. Specifically, we showed that DEL-1 is expressed by human and mouse osteoclasts and regulates their differentiation and resorptive function. Mechanistically, DEL-1 inhibited the expression of NFATc1, a master regulator of osteoclastogenesis, in a Mac-1 integrin- dependentmanner. In vivo mechanistic analysis has dissociated the anti-inflammatory from the anti-bone-resorptive action of DEL-1 and identified structural components thereof mediating these distinct functions. Locally administered human DEL-1 blocked inflammatory periodontal bone loss in nonhuman primates-a relevantmodel of human periodontitis. The ability of DEL-1 to regulate both upstream (inflammatory cell recruitment) and downstream (osteoclastogenesis) events that lead to inflammatory bone loss paves the way to a new class of endogenous therapeutics for treating periodontitis and perhaps other inflammatory disorders.
Details
Original language | English |
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Article number | 307ra155 |
Journal | Science Translational Medicine |
Volume | 7 |
Issue number | 307 |
Publication status | Published - 30 Sept 2015 |
Peer-reviewed | Yes |
External IDs
researchoutputwizard | legacy.publication#66928 |
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Scopus | 84942881294 |
PubMed | 26424570 |