Abstract
ObjectivesPreviously, we found that by regulating T helper (Th) cell polarization, calcitriol intervention inhibited lipopolysaccharide (LPS)‐induced alveolar bone loss in an animal periodontitis model, but the underlying cellular events remain unknown.Materials and methodsIn this study, mouse Th cells were incubated in an inflammatory environment in the presence of dendritic cells (DCs) and LPS. Then, the potential of the Th cells to undergo Th2/Th17 polarization, the RANKL expression of the polarized Th cells and the subsequent influences of the polarized Th cells on RAW264.7 cell osteoclastogenesis in response to calcitriol administration were assessed. Finally, the effects of calcitriol on antigen presentation by DCs during these cellular events were evaluated.ResultsIn response to calcitriol administration, Th cells in an inflammatory environment exhibited an enhanced potential for Th2 polarization along with a decreased potential for Th17 polarization. In addition, RANKL expression in Th17‐polarized cells was largely inhibited. Furthermore, inflammation‐induced osteoclastogenesis in RAW264.7 cells was suppressed following coculture with calcitriol‐treated Th cells. During these cellular events, increased expression of Th2 promoters (such as OX‐40L and CCL17) and decreased expression of Th17 promoters (such as IL‐23 and IL‐6) were found in DCs.ConclusionsCalcitriol can inhibit osteoclastogenesis in an inflammatory environment by changing the proportion and function of Th cell subsets. Our findings suggest that calcitriol may be an effective therapeutic agent for treating periodontitis.
Highlights
Chronic periodontitis is characterized by local inflammation-induced bone loss due to the interaction between the host defence mechanism and plaque bacteria on the supporting tissues of the teeth.[1,2] During this inflammatory process, the host inflammatory response inevitably exerts an impact that induces systematic skeletal changes in alveolar bone
We found that calcitriol could suppress LPSinduced bone loss and regulate T helper (Th) cell polarization in experimental periodontitis.[14]
Previous studies showed that Th17 cells are crucial resources of proinflammatory products, such as RANKL and IL-17, which could induce the resorption of bone,[37] and the tissue destruction of periodontitis is related to the decreased protective effect of the Th2 cell and its cytokine (IL-4).[4]
Summary
Chronic periodontitis is characterized by local inflammation-induced bone loss due to the interaction between the host defence mechanism and plaque bacteria on the supporting tissues of the teeth.[1,2] During this inflammatory process, the host inflammatory response inevitably exerts an impact that induces systematic skeletal changes in alveolar bone. In terms of the immune system network, T helper (Th) cells, the subsets of which are determined by immunity-associated antigen-presenting cells such as dendritic cells (DCs), can play both damaging and protective roles in bone loss by regulating the RANKLOPG system.[3,4] Classically, Th cells can be divided into four types (Th1, Th2, Th17 and regulatory T cell (Treg)) Among these types, Th17 subsets with proinflammatory and pro-osteoclastogenic characteristics are reported to enhance leucocyte influx into periodontal tissues and intensify bone lesions through osteoclast precursor maturation and enhanced local RANKL levels.[5,6,7] In contrast, the Th2 phenotype and its characteristic cytokine, IL-4, can attenuate periodontal tissue destruction by inhibiting proinflammatory cytokine and RANKL expression.[7,8,9,10,11] an increasing number of studies have found that the functions of Th cells are closely related to RANKL-induced osteoclast differentiation.[8,12,13] In this context, researchers have attempted to attenuate inflammation-induced tissue destruction by modulating Th cells towards anti-inflammatory polarization. Promoting Th2 polarization and attenuating Th17 polarization by using bioactive immunomodulator agents, such as calcitriol, may be a practical strategy to inhibit tissue destruction.[14,15,16]
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