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| Open AccessMarShie: a clearing protocol for 3D analysis of single cells throughout the bone marrow at subcellular resolution
Three-dimensional analysis of the intact bone marrow within whole long bones remains very challenging. Here, the authors present a method that stabilizes the marrow and provides subcellular resolution of fluorescent signals throughout the murine femur.
- Till Fabian Mertens
- , Alina Tabea Liebheit
- & Anja Erika Hauser
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| Open AccessEosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase
Eosinophils are traditional immune effectors involved in tissue homeostasis. In this study, eosinophils emerge as key regulators of bone homeostasis by interacting with osteoclasts, inhibiting their differentiation and pathological bone loss.
- Darja Andreev
- , Katerina Kachler
- & Aline Bozec
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| Open AccessLangerhans cells shape postnatal oral homeostasis in a mechanical-force-dependent but microbiota and IL17-independent manner
In postnatal life, oral mucosal immunity is shaped by microbiota and the interrelating immune cells. Here, the authors show that although microbial factors facilitate the differentiation of oral Langerhans cells, their function in surveillance of mucosal epithelial barriers and capacity to induce adaptive immunity is predominantly governed by masticatory mechanical forces.
- Yasmin Jaber
- , Yasmine Netanely
- & Avi-Hai Hovav
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| Open AccessInsights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
Osteoclasts are derived from circulating myeloid cells to mediate bone repair, maintenance and remodeling. Here, the authors show that the lung also recruits and reprograms monocytes and alveolar macrophages into osteoclast-like cells to clear pathogenic particles from the airspace.
- Yasuaki Uehara
- , Yusuke Tanaka
- & Francis X. McCormack
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| Open AccessOsteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection
MYD88 mediates the signal of bacterial infection. Here, in the context of periodontal infection, the authors show that the MYD88 pathway in osteocytes plays a dominant role in regulating osteolysis.
- Tetsuya Yoshimoto
- , Mizuho Kittaka
- & Yasuyoshi Ueki
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| Open AccessPeriosteal stem cells control growth plate stem cells during postnatal skeletal growth
Intramembranous and endochondral bone formation have been considered to be independent processes mediated by independent stem cells. Here the authors show that periosteal stem cells participate in both types of bone formation, supporting endochondral formation by producing Ihh.
- Masayuki Tsukasaki
- , Noriko Komatsu
- & Hiroshi Takayanagi
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| Open AccessInhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis
Periprosthetic osteolysis is a cause of arthroplasty failure without available therapies. Here the authors show that Annexin A1 (AnxA1) is involved in in periprosthetic osteolysis and exerts potential therapeutic effects through suppressing NFκB signaling and promoting the PPAR-γ pathway resulting in inhibition of inflammation and osteoclasts differentiation induced by wear debris.
- Hend Alhasan
- , Mohamad Alaa Terkawi
- & Norimasa Iwasaki
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| Open AccessTGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis
Mechanisms for inflammatory osteolysis are unclear. Here, Xia et al. find that TGFβ shifts the inflammatory action of TNF on macrophages to a potent osteoclastogenic function and identify a novel TGFβ/TNF-mediated non-canonical osteoclastogenic program.
- Yuhan Xia
- , Kazuki Inoue
- & Baohong Zhao
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Article
| Open AccessTRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration
Supplementation of magnesium (Mg2+) or its inclusion in biomaterials has beneficial effects for bone formation, but it has also been reported that it can have detrimental effects. Here, the authors analyse dose- and time-dependent effects of Mg2+ on bone regeneration and show that it can stimulate monocyte-macrophage lineage cells to support bone formation in the early phases of repair, but inhibit bone repair and mineralization in later stages by promoting a pro-inflammatory environment.
- Wei Qiao
- , Karen H. M. Wong
- & Kelvin W. K. Yeung
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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 AccessCalcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis
How extracellular calcium can trigger Nlrp3 inflammasome activation has been somewhat controversial and unclear. Here the authors show calciprotein particles are taken up by myeloid cells via calcium-sensing receptor-dependent macropinocytosis in response to high levels of extracellular Ca2+ and this pathway might be critical to inflammatory conditions.
- Elisabeth Jäger
- , Supriya Murthy
- & Ulf Wagner
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| Open AccessRegulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing
Aberrant tissue repair may result in heterotopic ossification (HO), but how this process is regulated by local inflammatory responses is still unclear. Here the authors show, using a mouse burn/trauma model, that TGFβ-producing monocytes/macrophages at the injury site contribute to HO induction, while CD47 activation helps antagonize this process.
- Michael Sorkin
- , Amanda K. Huber
- & Benjamin Levi
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| Open AccessPTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells
T cells are involved in the bone loss induced by parathyroid hormone (PTH), but their origin is unknown. Here, the authors show that the intestinal microbiota is required for PTH to induce bone loss and describes mechanisms for microbiota-mediated gut–bone crosstalk in mouse models of hyperparathyroidism.
- Mingcan Yu
- , Abdul Malik Tyagi
- & Roberto Pacifici
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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 AccessGM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis
Spondyloarthritis pathology is manifested by increased myeloid infiltration of the joints. Here the authors show that in a mouse model of spondyloarthritis, a single dose of a microbial ligand curdlan induces persistent extramedullary myelopoiesis in the spleen and joints, which is driven by GM-CSF and can be amplified by exogenous IL-33.
- Daniel Regan-Komito
- , James W. Swann
- & Thibault Griseri
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Article
| Open AccessA small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development
Loss of cartilage tissue is a hallmark of osteoarthritis. Here the authors show that BNTA, a small molecule identified in a chemical screen, promotes ECM generation in human osteoarthritic chondrocytes and cartilage explants, and suppresses pathology in a rat model of osteoarthritis.
- Yuanyuan Shi
- , Xiaoqing Hu
- & Yingfang Ao
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| Open AccessRORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients
The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.
- Koen Venken
- , Peggy Jacques
- & Dirk Elewaut
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| Open AccessB cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation
B cells contribute to rheumatoid arthritis pathogenesis and bone erosion, but the underlying mechanisms are still unclear. Here the authors show, using mouse models and patient tissues, that B cells directly inhibit osteoblast differentiation by producing CCL3 and TNF, thereby providing a potentially new direction for arthritis therapy.
- Wen Sun
- , Nida Meednu
- & Lianping Xing
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| Open AccessReciprocal inhibition of YAP/TAZ and NF-κB regulates osteoarthritic cartilage degradation
Inflammation can promote cartilage degradation by inducing matrix-degrading enzymes via NF-κB. Here the authors uncover reciprocal inhibition of Yap/Taz and NF-κB signaling though TAK1, and identify Yap activity as critical for maintenance of cartilage integrity in a mouse model of osteoarthritis.
- Yujie Deng
- , Jinqiu Lu
- & Kinglun Kingston Mak
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| Open AccessBone protection by inhibition of microRNA-182
Osteoclasts mediate bone disruption in a number of degenerative bone diseases. Here, the authors show that miR-182 regulates osteoclastogenesis via PKR and IFN-beta signaling, is correlated with rheumatoid arthritis, and that its ablation or inhibition is protective against bone erosion in mouse models of osteoporosis or inflammatory arthritis.
- Kazuki Inoue
- , Zhonghao Deng
- & Baohong Zhao
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| Open AccessHost defense against oral microbiota by bone-damaging T cells
IL-17-producing T cells are protective against infection, but the authors of this article previously showed that these cells also contribute to inflammatory bone destruction. Here they show in the context of periodontitis that microbiota-driven Th17-mediated bone destruction may actually be a physiological rather than a pathological process, as associated tooth loss prevents dissemination of oral bacteria.
- Masayuki Tsukasaki
- , Noriko Komatsu
- & Hiroshi Takayanagi
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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