Journal
JOURNAL OF IMMUNOLOGY
Volume 197, Issue 10, Pages 3871-3883Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1601114
Keywords
-
Categories
Funding
- National Institutes of Health [RO1 DE-03420, RO1 DE-018499, RO1 DE-019917, R56 DE 023807, RO1 DE025255]
- National Institute of Dental and Craniofacial Research [T32 DE 7327-12]
- Japan Society for the Promotion of Science [23689081, 25670841, 15K11376]
- German Society of Periodontology [2-RST-2013]
- Grants-in-Aid for Scientific Research [15K11376] Funding Source: KAKEN
Ask authors/readers for more resources
Host immune responses play a key role in promoting bone resorption in periodontitis via receptor activator of NF-kappa B ligand (RANKL)-dependent osteoclastogenesis. Both membrane-bound RANKL (mRANKL) expressed on lymphocytes and soluble RANKL (sRANKL) are found in periodontal lesions. However, the underlying mechanism and cellular source of sRANKL release and its biological role in periodontitis are unclear. TNF-alpha-converting enzyme (TACE) is reported to cleave the following: 1) precursor TNF-alpha with release of mature, soluble TNF-alpha and 2) mRANKL with release of sRANKL. Both soluble TNF-alpha and sRANKL are found in the periodontitis lesion, leading to the hypothesis that TACE expressed on lymphocytes is engaged in RANKL shedding and that the resulting sRANKL induces osteoclastogenesis. In the current study, upon stimulating PBLs with mitogens in vitro, RANKL expression, sRANKL secretion, and TACE expression were all upregulated. Among the four putative mRANKL sheddases examined in neutralization assays, TACE was the only functional sheddase able to cleave mRANKL expressed on PBL. Moreover, PBL culture supernatant stimulated with mitogens in the presence of anti-TACE Ab or anti-RANKL Ab showed a marked reduction of osteoclastogenesis from osteoclast precursors, indicating that TACE-mediated sRANKL may possess sufficient osteoclastogenic activity. According to double-color confocal microscopy, B cells expressed a more pronounced level of RANKL and TACE expression than T cells or monocytes in periodontally diseased gingiva. Conditioned medium of patients' gingival lymphocyte culture increased in vitro osteoclastogenic activity, which was suppressed by the addition of anti-TACE Ab and anti-RANKL Ab. Therefore, TACE-mediated cleavage of sRANKL from activated lymphocytes, especially B cells, can promote osteoclastogenesis in periodontitis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available