Osteoimmunology

  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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