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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Determinants of Periodontal/Periapical Lesion Stability and Progression

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Author(s):
Cavalla, F. [1] ; Letra, A. [2, 3, 4] ; Silva, R. M. [5, 3, 4] ; Garlet, G. P. [6]
Total Authors: 4
Affiliation:
[1] Univ Chile, Sch Dent, Dept Conservat Dent, Santiago - Chile
[2] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Dept Diagnost & Biomed Sci, Houston, TX 77030 - USA
[3] Univ Texas Hlth Sci Ctr Houston, Pediat Res Ctr, McGovern Med Sch, Houston, TX 77030 - USA
[4] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Ctr Craniofacial Res, Houston, TX 77030 - USA
[5] Univ Texas Hlth Sci Ctr Houston, Dept Endodont, Sch Dent, Houston, TX 77030 - USA
[6] Sao Paulo Univ FOB USP, Dept Biol Sci, Sch Dent Bauru, OSTEOimmunol Lab, Bauru, SP - Brazil
Total Affiliations: 6
Document type: Review article
Source: JOURNAL OF DENTAL RESEARCH; v. 100, n. 1 AUG 2020.
Web of Science Citations: 0
Abstract

Periodontal and periapical lesions are infectious inflammatory osteolitytic conditions in which a complex inflammatory immune response mediates bone destruction. However, the uncertainty of a lesion's progressive or stable phenotype complicates understanding of the cellular and molecular mechanisms triggering lesion activity. Evidence from clinical and preclinical studies of both periodontal and periapical lesions points to a high receptor activator of NF-kappa B ligand/osteoprotegerin (RANKL/OPG) ratio as the primary determinant of osteolytic activity, while a low RANKL/OPG ratio is often observed in inactive lesions. Proinflammatory cytokines directly modulate RANKL/OPG expression and consequently drive lesion progression, along with pro-osteoclastogenic support provided by Th1, Th17, and B cells. Conversely, the cooperative action between Th2 and Tregs subsets creates an anti-inflammatory and proreparative milieu associated with lesion stability. Interestingly, the trigger for lesion status switch from active to inactive can originate from an unanticipated RANKL immunoregulatory feedback, involving the induction of Tregs and a host response outcome with immunological tolerance features. In this context, dendritic cells (DCs) appear as potential determinants of host response switch, since RANKL imprint a tolerogenic phenotype in DCs, described to be involved in both Tregs and immunological tolerance generation. The tolerance state systemically and locally suppresses the development of exacerbated and pathogenic responses and contributes to lesions stability. However, immunological tolerance break by comorbidities or dysbiosis could explain lesions relapse toward activity. Therefore, this article will provide a critical review of the current knowledge concerning periodontal and periapical lesions activity and the underlying molecular mechanisms associated with the host response. Further studies are required to unravel the role of immunological responsiveness or tolerance in the determination of lesion status, as well as the potential cooperative and/or inhibitory interplay among effector cells and their impact on RANKL/OPG balance and lesion outcome. (AU)

FAPESP's process: 15/24637-3 - MSCs and m2 as determinants of the constructive or destructive nature of inflammatory microenvironments associated with bone tissue
Grantee:Gustavo Pompermaier Garlet
Support Opportunities: Research Projects - Thematic Grants