DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates.

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-dependent manner. 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 relevant model 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.

journal_name

Sci Transl Med

authors

Shin J,Maekawa T,Abe T,Hajishengallis E,Hosur K,Pyaram K,Mitroulis I,Chavakis T,Hajishengallis G

doi

10.1126/scitranslmed.aac5380

subject

Has Abstract

pub_date

2015-09-30 00:00:00

pages

307ra155

issue

307

eissn

1946-6234

issn

1946-6242

pii

7/307/307ra155

journal_volume

7

pub_type

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