Pro-inflammatory Cytokines Modulating Osteoclast Differentiation and Function

Semun Seong; Jung Ha Kim; Nacksung Kim

doi:10.4078/jrd.2016.23.3.148

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Seong, Kim, and Kim: Pro-inflammatory Cytokines Modulating Osteoclast Differentiation and Function

Review Article

J Rheum Dis 2016;23(3):148-153.

Published online: 31 October 2016

DOI: https://doi.org/10.4078/jrd.2016.23.3.148

Pro-inflammatory Cytokines Modulating Osteoclast Differentiation and Function

Semun Seong^1,², Jung Ha Kim¹, Nacksung Kim^1,²

¹Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea

²Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Korea

Corresponding to: Nacksung Kim, Department of Pharmacology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea. E-mail: nacksung@jnu.ac.kr

Received 2 June 20167 June 2016 Accepted 11 June 2016

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In general, bone homeostasis is maintained through the balance between bone formation and resorption. Disruption in this balance results in bone-related diseases such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Often, enhanced osteoclastogenesis is followed by accelerated bone resorption that is induced by pro-inflammatory cytokines in osteoporosis or rheumatoid arthritis, and leads to bone destruction. In this review study, factors involved in osteoclast differentiation and function are discussed, and how the prevention of such factors is effective in ameliorating bone loss in osteoporosis or rheumatoid arthritis.

Keywords: Bone and bones, Osteoclasts, Rheumatoid arthritis, Cytokines

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Figure 1.

Roles of proinflammatory cytokines in osteoclastogenesis. Pro-inflammatory cytokines are produced from various immune cells including T cells, B cells, macrophages, dendritic cells, FLS, etc. Proinflammatory cytokines induce osteoclastogenesis either dependent or independent of the RANKL-RANK signaling pathway. FLS: fibroblast-like synoviocytes, IL: interleukin, RANKL: receptor activator of nuclear factor kappa-B ligand, TNF-α: tumor necrosis factor alpha.

Table 1.

Roles of pro-inflammatory cytokines in osteoclastogenesis

Cytokines	Effects on osteoclasts	Effects on osteoblasts	Effects of antibody/blockade	Sources
TNF-α	Enhances osteoclastogenesis independent of RANKL-RANK signaling pathway Exhibits pro-osteoclastogenic effects synergistically with IL-1	Upregulates M-CSF and RANKL in osteoblasts and osteocytes Inhibits osteoblastogenesis and nodule formation Induces Dkk-1, Wnt antagonist, to inhibit osteoblastogenesis	Inhibitor utilization alleviates synovial inflammation and join erosion Prevents systemic bone loss	Macrophages
IL-1	Enhances osteoclastogenesis and prevents osteoclast apoptosis by upregulating RANKL expression and stimulating M-CSF production Enhances osteoclastogenesis and bone resorption Mediates TNF-α-induced osteoclastogenesis	Stimulates RANKL production	Decreases cartilage damage and bone resorption	Macrophages
IL-6	Dual roles on osteoclasts; induces bone resorption Inhibits RANK signaling in osteoclast progenitors in the absence of supporting cells	Induces RANKL synthesis in osteoblasts	Suppresses RANKL-stimulated osteoclast differentiation and bone resorption	T cells Macrophages Synovial fibroblasts
IL-17	Supports osteoclastogenesis dependent of RANKL-RANK signaling pathway Enhances the sensitivity of osteoclast precursors to RANKL	Upregulates RANKL expression	Reduces bone destruction and joint erosion	Th 17 cells
IL-18	Suppresses osteoclastogenesis but involved in bone destruction Stimulates osteoclastogenesis by upregulating RANKL production from T cells	Increases OPG expression in osteoblasts	Decreases inflammation and cartilage degradation Inhibits TNF-α, IL-6, and IFN-gamma secretion	Macrophages Dendritic cells
IL-23	Enhances osteoclastogenesis Upregulates RANK expression to induce osteoclastogenesis	Direct effect of IL-23 on osteoblasts is unknown	Suppresses osteoclastogenesis, inflammation, and bone destruction	Macrophages Osteoclasts

IFN: interferon, IL: interleukin, M-CSF: macrophage-colony stimulating factor, OPG: osteoprotegerin, RANKL: receptor activato of nuclear factor kappa-B ligand, Th 17: T helper 17, TNF-α: tumor necrosis factor alpha.

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