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

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Science Translational Medicine  30 Sep 2015:
Vol. 7, Issue 307, pp. 307ra155
DOI: 10.1126/scitranslmed.aac5380

DELivering new therapies for chronic inflammation

Chronic inflammation is prevalent in nearly half of adult teeth and gums in the U.S. population, and this so-called periodontitis can increase a patient’s risk of developing other inflammatory diseases in the heart (atherosclerosis) and joints (rheumatoid arthritis). Shin et al. capitalized on the natural anti-inflammatory activity of the protein DEL-1, finding that it not only blocked excessive immune cell infiltration into the periodontium but also had innate anti-osteoclastogenic activity; that is, it stopped bone loss by interrupting the signaling pathways to osteoclasts, the bone-resorbing cells. In vitro, in human and mice osteoclast precursor cells, DEL-1 prevented osteoclast differentiation by inhibiting NFATc1 activity. In vivo, in mouse and nonhuman primate models of periodontitis, giving DEL-1 locally reduced inflammation and tissue destruction, thus halting any tissue loss. The mechanism appears to be two-pronged: working “upstream” in disease signaling pathways to prevent inflammatory cell recruitment to the teeth and gums, as well as acting “downstream” to stop osteoclastogenesis. With data in a monkey model that represents the human disease, anatomy, and immune system closely, it is likely that DEL-1–based therapeutics could translate soon once safety of this endogenous molecule is confirmed.

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