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Effects of retinoids on physiologic and inflammatory osteoclastogenesis in vitro

Journal article
Authors Vikte Lionikaite
Anna Westerlund
H. H. Conaway
Petra Henning
Ulf H Lerner
Published in Journal of leukocyte biology
Volume 104
Issue 6
Pages 1133-1145
ISSN 1938-3673
Publication year 2018
Published at Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 1133-1145
Language en
Links dx.doi.org/10.1002/JLB.3A0318-094RR
Keywords inflammation, LPS, osteoclasts, RANKL, TNF, vitamin A
Subject categories Orthopedics, Rheumatology and Autoimmunity

Abstract

Increased intake of vitamin A (retinoids) is associated with decreased bone mass and increased fracture risk in humans. Mechanistic studies in rodents have shown that hypervitaminosis A results in decreased bone mass caused by an increase in periosteal osteoclasts while simultaneously decreasing endocortic osteoclasts. In vivo and ex vivo bone organ cultures have demonstrated that excess retinoids increase osteoclast formation due to increased receptor activator of nuclear factor kappa B-ligand (RANKL) expression. In vitro, studies using murine bone marrow macrophages (BMM) have shown that retinoids inhibit osteoclast formation induced by recombinant RANKL. These opposing in vivo/ex vivo versus in vitro effects may elucidate why excess retinoids affect periosteal and endocortic osteoclast formation differently. In addition, it has been reported that retinoids can inhibit osteoclast formation under inflammatory conditions such as experimentally induced arthritis in mice. In the present study, we have compared the effect of all-trans-retinoic acid (ATRA) on physiologically and inflammatory induced osteoclastogenesis. ATRA inhibited physiologically induced (RANKL) osteoclast formation of human peripheral blood monocytes and mouse BMM as well as human monocytes stimulated with the pro-inflammatory compounds, TNF-α and LPS. The inhibition was due to impeded differentiation, rather than fusion, of mononucleated progenitor cells. ATRA disrupted differentiation by interfering with osteoclastogenic intracellular signaling. In line with this view, overexpression of Tnfrsf11a (encodes for RANK) in BMM could not overcome the inhibition of osteoclastogenesis by ATRA. The data suggest that ATRA inhibits both physiologic and inflammatory osteoclast differentiation of progenitors from the bone marrow and peripheral blood. ©2018 Society for Leukocyte Biology.

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