Research news: DEL-1's one-two punch may pave the way to a new class of endogenous therapeutics for treating periodontitis and other inflammatory disorders

Oct. 10, 2015
Researchers have recently identified a mechanism within DEL-1 whereby bone loss is stopped and immune cell infliltration into the periodontium is blocked. This news offers great hope for a new class of therapeutics to treat periodontitis and possibly other inflammatory disorders as well.

It is well supported in the literature that untreated periodontitis can increase an individual’s chance of developing other inflammatory diseases such as cardiovascular disease and rheumatoid arthritis. Since such a large number of people suffer from rampant caries, the ongoing research into reducing inflammation is, for a number of reasons, a justifiable focus in the quest to promote oral-systemic health.

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On the scientific front, researchers have identified a novel regulatory mechanism of DEL-1 (developmental endothelial locus-1)—an endothelial cell-secreted protein that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin-dependent leukocyte recruitment and inflammation in various tissues—in osteoclast biology. According to a summary published by the American Association for the Advancement of Science, study authors Shin, et al. (1) “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.

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“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.” (1)

Read the abstract from PubMed here.

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1. Shin J, Maekawa T, Abe T, Hajishengallis E, Hosur K, Pyaram K, Mitroulis I, Chavakis T, Hajishengallis G. DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates. Sci Transl Med. 2015;7(307):307ra155. doi: 10.1126/scitranslmed.aac5380.