Magnolol Inhibits Osteoclast Differentiation via Suppression of RANKL Expression

Youn-Hwan Hwang,Rajeong Kim,Taesoo Kim,Hyunil Ha

doi:10.3390/molecules23071598

Youn-Hwan Hwang, Rajeong Kim + Show 2 more

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https://doi.org/10.3390/molecules23071598

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Journal: Molecules	Publication Date: Jul 2, 2018
Citations: 15	License type: CC BY 4.0

Affiliation: Korea Institute of Oriental Medicine

Abstract

Magnolol, a compound from the traditional Korean herb Magnolia sp., has been exhaustively investigated as a therapeutic agent against several diseases including systemic and local inflammation. We examined the effects of magnolol on osteoclastic differentiation associated with inflammation. Magnolol markedly reduced interleukin (IL)-1-induced osteoclast formation in co-cultures of murine osteoblasts and bone marrow cells, whereas it had no effect on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in bone marrow macrophage cultures. In osteoblasts, magnolol markedly inhibited both the up-regulation of RANKL expression and the production of prostaglandin E2 (PGE2) in response to IL-1 treatment. Addition of exogenous PGE2 reversed the inhibitory effects of magnolol on IL-1-induced RANKL expression in osteoblasts and osteoclast formation in co-cultures. Magnolol inhibited IL-1-induced PGE2 production, at least in part by suppressing cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that magnolol inhibits IL-1-induced RANKL expression in osteoblasts through suppression of COX-2 expression and PGE2 production, resulting in inhibition of osteoclast differentiation in co-cultures.

Highlights

Osteoclasts are multinucleated, bone-resorbing cells produced via differentiation from monocyte/macrophage lineage cells
We aimed to investigate the effects of magnolol on osteoclast differentiation associated with inflammation using a co-culture system comprising mouse osteoclast differentiation associated with inflammation using a co-culture system comprising mouse osteoblasts and bone marrow cells with the pro-inflammatory cytokine IL-1
Various osteotropic factors factorssuch suchasasIL-1, IL-1, parathyroid hormone, 1,25-dihydroxyvitamin expression on osteoblasts leading to the differentiation of and prostaglandin E2 (PGE2 ) induce RANKL expression on osteoblasts leading to the differentiation osteoclast precursors into osteoclasts in a co-culture system comprising osteoblasts and osteoclast of osteoclast precursors into osteoclasts in a co-culture system comprising osteoblasts and osteoclast precursors [3]

Summary

Introduction

Osteoclasts are multinucleated, bone-resorbing cells produced via differentiation from monocyte/macrophage lineage cells. Ligand (RANKL), expressed on osteoclast-supporting cells including osteoblasts and stromal cells, is an essential cytokine that induces osteoclast differentiation and activation by binding to its receptor. RANK expressed on osteoclast precursors and osteoclasts [1]. A key mediator of local and systemic bone loss, is linked to an increased risk of osteoporotic fracture in patients with arthritis, periodontitis, and inflammatory bowel diseases, and in healthy individuals with low-grade inflammation [2]. Among pro-inflammatory mediators, interleukin (IL)-1 plays a key role in bone destruction under pathological conditions such as rheumatoid arthritis and osteoporosis [3]. IL-1 can directly stimulate osteoclastic bone resorption through multiple mechanisms including promotion of osteoclast precursor fusion, enhancement of bone-resorbing activity of osteoclasts, and prolongation of osteoclast survival [4,5]

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