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| Open AccessSelenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts
Selenoproteins containing selenium have a variety of physiological functions including redox homeostasis and thyroid hormone metabolism. Here, the authors show that RANKL-dependent repression of selenoprotein W regulates cell fusion during osteoclast differentiation and bone remodelling in mice.
- Hyunsoo Kim
- , Kyunghee Lee
- & Daewon Jeong
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| Open AccessOsteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins
The innate immune system and inflammation modulate bone homeostasis through complex regulation of bone remodelling cells including osteoblasts and osteoclasts. Here, the authors show that the type I interferon pathway and guanylate binding proteins functionally limit bone loss by inhibiting osteoclast functions.
- David E. Place
- , R. K. Subbarao Malireddi
- & Thirumala-Devi Kanneganti
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| Open AccessEnvironmental arginine controls multinuclear giant cell metabolism and formation
Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.
- Julia S. Brunner
- , Loan Vulliard
- & Gernot Schabbauer
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| Open AccessDirect cell–cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo
Communication between osteoblasts and osteoclasts is essential for bone homeostasis, but the mode of interaction is unclear. The authors use intravital two-photon microscopy in mice to show that these cells directly interact, regulating activity of osteoclasts, and that the interaction is modulated by parathyroid hormone administration.
- Masayuki Furuya
- , Junichi Kikuta
- & Masaru Ishii
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| Open AccessShort-chain fatty acids regulate systemic bone mass and protect from pathological bone loss
Short-chain fatty acids (SCFA) are a main class of metabolites derived from fermentation of dietary fibre in the intestine. Here, the authors show that dietary administration of SCFA is associated with inhibition of osteoclast differentiation, increased bone mass, and reduced pathological bone loss in mice.
- Sébastien Lucas
- , Yasunori Omata
- & Mario M. Zaiss
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| Open AccessDJ-1 controls bone homeostasis through the regulation of osteoclast differentiation
Osteoclasts are involved in arthritis, and their differentiation depends on RANKL signaling. The author show that the ROS-scavenging protein DJ-1 negatively regulates RANKL signaling and that its ablation increases osteoclast numbers and exacerbates bone damage in mouse models of arthritis.
- Hyuk Soon Kim
- , Seung Taek Nam
- & Wahn Soo Choi
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| Open AccessSuccinate and its G-protein-coupled receptor stimulates osteoclastogenesis
Bone loss is common in patients with diabetes, but the underlying molecular and cellular mechanisms are unclear. Here the authors show high succinate levels in mice with type 2 diabetes and that succinate can signal through succinate receptor 1 on osteoclasts to induce bone resorption.
- Yuqi Guo
- , Chengzhi Xie
- & Xin Li
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| Open AccessNELL-1 in the treatment of osteoporotic bone loss
The growth factor NELL-1 induces bone formation during development, but its role in osteoporosis is unknown. This study shows that NELL-1 binding to integrin ß1 induces Wnt/ß-catenin signalling in the bone and restores bone mineral density in osteoporotic mice and sheep, suggesting the therapeutic potential of NELL-1 for the treatment of bone loss.
- Aaron W. James
- , Jia Shen
- & Chia Soo
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| Open AccessGlycosylation of immunoglobulin G determines osteoclast differentiation and bone loss
The IgG sugar moiety modulates the binding of immune complexes to their Fcγ receptors resulting in pro- or anti-inflammatory response. This study shows that IgG sialylation also affects osteoclastogenesis and bone mass in mice and humans, identifying a new link between bone and the immune system.
- Ulrike Harre
- , Stefanie C. Lang
- & Georg Schett
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Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation
Small-molecule C21 inhibits Rac GTPase activation by Dock5, which decreases osteoclast activity in vitro. Using three mouse models where bone loss is caused by hyperactive osteoclasts, Vives et al. show that C21 treatment safely and efficiently prevents osteoporosis while preserving bone formation.
- Virginie Vives
- , Gaëlle Cres
- & Anne Blangy
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Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation
Epigenetic changes during the differentiation of bone-resorbing cells have important implications in bone remodelling. Here the authors target this pathway with I-BET151, an inhibitor of bromo and extra-terminal proteins that inhibits expression of the MYC-NFAT axis and suppresses bone loss in multiple mouse models.
- Kyung-Hyun Park-Min
- , Elisha Lim
- & Lionel B Ivashkiv
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Article
| Open AccessFoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation
Osteoclasts are bone-resorbing cells responsible for the loss of bone mass in diseases such as osteoporosis. Here the authors show that osteoclast proliferation and survival is regulated by FoxO family transcription factors, which control levels of the signalling molecule hydrogen peroxide.
- Shoshana M. Bartell
- , Ha-Neui Kim
- & Maria Almeida