The Role of Inflammatory Cytokines and the RANKL-RANK-OPG Molecular Triad in Periodontal Bone Loss-A Review

Prathiba Chichurakanahalli Srinivasan

doi:10.4172/2155-9899.s13-007

Abstract

Periodontal diseases are chronic inflammatory disorders involving the supporting structures of the teeth. Connective tissue destruction and loss of bone support of the dentition are key features of this disease. Early studies have revealed that biofilm plaque accumulation in the dentogingival area is the primary etiological factor of periodontal diseases. Recent research has not only reinforced the bacterial etiology of periodontal disease, but has also emphasized the role of inflammation in this pathologic process. The host mounts an immune-inflammatory response to combat the bacterial attack. The host response is like a double-edged sword. It eliminates the offending pathogens, but overstimulation and amplification of the same leads to tissue destruction and bone loss. In the mid- 1990s, extensive research in the field of bone biology led to the discovery of the RANKL-RANK-OPG molecular triad. This article explores the mechanisms by which inflammatory host response leads to alveolar bone loss-the role of cytokines, factors that stimulate osteoclastogenesis via the RANKL-RANK-OPG pathway and how inflammation interferes with the uncoupling of bone formation and bone resorption. In addition to the conventional therapeutic modalities aimed at eliminating the microbes, additional therapeutic strategies that interfere with the RANKL-RANKOPG axis may have a protective effect on the bone loss.

Highlights

Periodontal diseases, which are chronic inflammatory disorders localized to the attachment structures of the teeth, are considered to be the major cause of tooth loss in adults and the most prevalent form of bone pathology in humans [1]
The results revealed increased periodontal bone loss in these mice compared to wild-type mice, suggesting that chemokines and IL-17 are important in protecting host against pathogen-initiated bone loss
Using expression cloning and OPG as a probe, both the groups quickly identified its ligand, which they termed OPG ligand [40] and osteoclast differentiation factor [41] respectively. This ligand turned out to be identical to a member of the tumor necrosis factor (TNF) ligand family, which had been identified in the preceding year as receptor activator of nuclear factor-kappa B ligand (RANKL) [42] and TNF-related activation induced cytokine (TRANCE) [43]

Summary

Introduction

Periodontal diseases, which are chronic inflammatory disorders localized to the attachment structures of the teeth, are considered to be the major cause of tooth loss in adults and the most prevalent form of bone pathology in humans [1]. Using expression cloning and OPG as a probe, both the groups quickly identified its ligand, which they termed OPG ligand [40] and osteoclast differentiation factor [41] respectively This ligand turned out to be identical to a member of the TNF ligand family, which had been identified in the preceding year as RANKL [42] and TNF-related activation induced cytokine (TRANCE) [43]. Studies have revealed that during inflammatory response, cytokines, chemokines and other mediators stimulate periosteal osteoblasts, altering the expression levels of receptor activator of nuclear factorkappa B ligand (RANKL) on the osteoblast surface [9,49]. Teng et al in their study demonstrated the role of CD4+ T cells in mediating periodontal bone loss They found that administration of RANK ligand inhibitor; osteoprotegerin reduced osteoclastogenesis and inhibited alveolar bone destruction [55]. The up-regulated DKK-1 promotes bone resorption and blocks bone

Study Method

Conclusion