Determinants of Periodontal/Periapical Lesion Stability and Progression

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-κB 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.

Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement

“…Osteoprotegerin (OPG), which functions as a decoy receptor of RANKL and can be released from osteoblasts as well as periodontal ligament (PDL) fibroblasts, protects bone from excessive resorption by binding to RANKL and preventing its binding to the membrane-bound RANK receptor on osteoclast precursor cells and thus their differentiation and fusion to active bone-resorbing osteoclasts [9]. In this regard, it is not the absolute expression of RANKL that is decisive for osteoclast activity, but rather the ratio of RANKL to OPG expression, both for orthodontic tooth movement [2], which requires controlled osteoclastogenesis and osteoclast activity in the direction of tooth movement, as well as periodontitis [10,11]. A recent systematic review reports that (pre)clinical evidence regarding periapical as well as periodontal lesions hints at an increase of the RANKL/OPG ratio as a primary determinant of osteolytic activity in the etiopathology of periodontitis, whereas a decreased RANKL/OPG ratio seems to be associated with inactive lesions [11].…”

“…In this regard, it is not the absolute expression of RANKL that is decisive for osteoclast activity, but rather the ratio of RANKL to OPG expression, both for orthodontic tooth movement [2], which requires controlled osteoclastogenesis and osteoclast activity in the direction of tooth movement, as well as periodontitis [10,11]. A recent systematic review reports that (pre)clinical evidence regarding periapical as well as periodontal lesions hints at an increase of the RANKL/OPG ratio as a primary determinant of osteolytic activity in the etiopathology of periodontitis, whereas a decreased RANKL/OPG ratio seems to be associated with inactive lesions [11]. Thus, the RANKL/OPG system plays a crucial role both in orthodontic tooth movement as well as in the etiopathology of periodontitis [11,12].…”

“…A recent systematic review reports that (pre)clinical evidence regarding periapical as well as periodontal lesions hints at an increase of the RANKL/OPG ratio as a primary determinant of osteolytic activity in the etiopathology of periodontitis, whereas a decreased RANKL/OPG ratio seems to be associated with inactive lesions [11]. Thus, the RANKL/OPG system plays a crucial role both in orthodontic tooth movement as well as in the etiopathology of periodontitis [11,12]. Apart from the RANKL/OPG system, a distinct remodelling of the extracellular matrix (ECM) of the PDL is also required for OTM, which seems to be primarily controlled by different matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)-both released by PDL fibroblasts upon force application [13].…”

Immunohistochemical expression of macrophages in chronic periapical lesions

“…Periapical granulomas (PGs) and radicular cysts (RCs) are osteolytic inflammatory lesions that commonly affect the jaws (Koivisto et al 2012), in which a complex inflammatory immune response leads to the bone destruction (Cavalla et al 2021;Maia et al 2020). These lesions are characterized by the presence of a mononuclear inflammatory infiltrate consisting of lymphocytes, plasma cells, mast cells, and macrophages (Leonardi et al 2005).…”

Use of low-power laser as an adjunct in endodontic treatment of teeth with internal resorption and apical lesion

“…Las lesiones apicales son afecciones osteolíticas inflamatorias infecciosas en las que se produce una respuesta inmunitaria inflamatoria y genera destrucción ósea (Cavalla et al, 2020). La cicatrización favorable en dientes con lesiones apicales puede tardar de 6 meses hasta 2 años.…”