Effect of interleukin‐10 on gene expression of osteoclastogenic regulatory molecules in the rat dental follicle

Abstract

The aim of this study was to determine the effect of interleukin-10 (IL-10) on the gene expression of osteoclastogenic regulatory molecules in rat dental follicle cells. Interleukin-10 is an anti-inflammatory cytokine that inhibits alveolar bone resorption, but the molecular basis for this is unknown. Alveolar bone resorption is required for tooth eruption and the dental follicle functions to regulate the osteoclastogenesis needed for eruption. It does this by regulating its expression of receptor activator of nuclear factor-kappa B ligand (RANKL), colony-stimulating factor-1 (CSF-1), and osteoprotegerin (OPG). In this study, dental follicle cells were treated with IL-10, and the effect on gene expression of CSF-1, RANKL, and OPG was measured by reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-10 enhanced the expression of OPG and down-regulated the expression of RANKL and CSF-1. Laser capture microdissection was carried out to detect IL-10 gene expression in the dental follicle. Knockdown of the IL-10 gene expression in the follicle cells was accomplished using a short interfering RNA (siRNA) targeting IL-10 mRNA. In these knockdowns, RANKL expression was increased and OPG expression was decreased. All of these results suggest that IL-10 inhibits bone resorption by up-regulating OPG expression while down-regulating expression of RANKL and CSF-1.

IL-27 suppresses RANKL expression in CD4+ T cells in part through STAT3

“…This may be consistent with the recent report that Th17 cells differentiated by the combination of TGF-␤1 and IL-6 produce not only IL-17 but also IL-10 and therefore that these Th17 cells are not able to mediate pathogenic function [37]. Indeed, IL-10 was previously reported to inhibit bone resorption by up-regulating the expression of osteoprotegerin (OPG), which is a natural antagonist of RANKL, while down-regulating expression of RANKL and colony-stimulating factor-1 (CSF-1) [38]. IL-27 also has an ability to induce IL-10 production (Fig.…”

Effects of Local Antibiotic Delivery from Porous Space Maintainers on Infection Clearance and Induction of an Osteogenic Membrane in an Infected Bone Defect

“…In vitro work in human and rat dental cells has demonstrated that IL-10 has antiosteoclastogenic properties by means of increasing OPG and decreasing RANKL mRNA expression, and the high levels of IL-10 observed in the +Inc/-Abx group may contribute to unexpectedly low RANKL production. 35,36 However, it is also possible that analysis of the membrane does not fully represent the profile of RANKL expression. Previous in vitro work in human and murine osteoblasts has shown that RANKL is upregulated in response to S. aureus infection, 18,19,37 and other studies have indicated that osteocytes, as opposed to osteoblasts or bone marrow stromal cells, are the dominant source of RANKL.…”

Immunology of Gut-Bone Signaling

“…IL-10 directly suppresses osteoclast formation by reducing nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) expression and its translocation to the nucleus (133) and by suppressing c-Fos and c-Jun (134). Indirectly IL-10 has been shown to modulate osteoclast formation by increasing gene expression of OPG and decreasing RANKL gene expression in dental follicle cells (135). …”