Rheumatology

  • Article | | open

    Mammalian joints have poor regenerative capacity following amputation. Here, the authors show that in mice, stimulation of the amputation wound with BMP2 and BMP9 stimulates regeneration of a synovial joint that includes bone, cartilage and a synovial cavity.

    • Ling Yu
    • , Lindsay A. Dawson
    • , Mingquan Yan
    • , Katherine Zimmel
    • , Yu-Lieh Lin
    • , Connor P. Dolan
    • , Manjong Han
    •  & Ken Muneoka
  • Article | | open

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    • , Jack A Bibby
    • , Wing Wu
    • , Klaus Stensgaard Frederiksen
    • , Ceri A. Roberts
    • , Zoe Hall
    • , Gaelle LeFriec
    • , Kevin A. Robertson
    • , Paul Lavender
    • , Jens Gammeltoft Gerwien
    • , Leonie S. Taams
    • , Julian L. Griffin
    • , Emanuele de Rinaldis
    • , Lisa G. M. van Baarsen
    • , Claudia Kemper
    • , Peter Ghazal
    •  & Andrew P. Cope
  • Article | | open

    Insulin resistance is associated with development of type 2 diabetes. Here the authors show that TAZ interacts with c-Jun and Tead4, inducing expression of the insulin receptor substrate 1 (IRS1) leading to increased glucose uptake in muscle, and that its activity is counteracted by statin administration.

    • Jun-Ha Hwang
    • , A Rum Kim
    • , Kyung Min Kim
    • , Jung Il Park
    • , Ho Taek Oh
    • , Sung A Moon
    • , Mi Ran Byun
    • , Hana Jeong
    • , Hyo Kyung Kim
    • , Michael B. Yaffe
    • , Eun Sook Hwang
    •  & Jeong-Ho Hong
  • Article | | open

    Osteoarthritis (OA) is associated with cartilage degeneration, and no effective therapy exists. Here, the authors show that the HPIP protein modulates OA progression by regulating Wnt signaling, and that its knockdown in joints via AAV-mediated gene silencing attentuates pathology.

    • Quanbo Ji
    • , Xiaojie Xu
    • , Lei Kang
    • , Yameng Xu
    • , Jingbo Xiao
    • , Stuart B. Goodman
    • , Xiang Zhu
    • , Wenchao Li
    • , Juan Liu
    • , Xu Gao
    • , Zhifeng Yan
    • , Yuxuan Zheng
    • , Zheng Wang
    • , William J. Maloney
    • , Qinong Ye
    •  & Yan Wang
  • Article | | open

    Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice.

    • Hao Chen
    • , Bo Hu
    • , Xiao Lv
    • , Shouan Zhu
    • , Gehua Zhen
    • , Mei Wan
    • , Amit Jain
    • , Bo Gao
    • , Yu Chai
    • , Mi Yang
    • , Xiao Wang
    • , Ruoxian Deng
    • , Lei Wang
    • , Yong Cao
    • , Shuangfei Ni
    • , Shen Liu
    • , Wen Yuan
    • , Huajiang Chen
    • , Xinzhong Dong
    • , Yun Guan
    • , Huilin Yang
    •  & Xu Cao
  • Article | | open

    Estrogen promotes negative energy balance and preserves skeletal physiology. Here the authors show that loss of estrogen signalling after ablating estrogen receptor alpha (ERa) in specific hypothalamic neuronal populations leads to a marked sex-dependent increase in bone mass in female mice.

    • Candice B. Herber
    • , William C. Krause
    • , Liping Wang
    • , James R. Bayrer
    • , Alfred Li
    • , Matthew Schmitz
    • , Aaron Fields
    • , Breanna Ford
    • , Zhi Zhang
    • , Michelle S. Reid
    • , Daniel K. Nomura
    • , Robert A. Nissenson
    • , Stephanie M. Correa
    •  & Holly A. Ingraham
  • Article | | open

    Osteoarthritis is characterised by degeneration of joint cartilage. Here the authors show that the RNA-binding protein ZFP36L1 is upregulated in chondrocytes of humans and mice with osteoarthritis, and that its knockdown in mouse joints protects chondrocytes against apoptosis by modulating the function of heat shock proteins.

    • Young-Ok Son
    • , Hyo-Eun Kim
    • , Wan-Su Choi
    • , Churl-Hong Chun
    •  & Jang-Soo Chun
  • Article | | open

    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
    • , Céline Mortier
    • , Mark E. Labadia
    • , Tine Decruy
    • , Julie Coudenys
    • , Kathleen Hoyt
    • , Anita L. Wayne
    • , Robert Hughes
    • , Michael Turner
    • , Sofie Van Gassen
    • , Liesbet Martens
    • , Dustin Smith
    • , Christian Harcken
    • , Joseph Wahle
    • , Chao-Ting Wang
    • , Eveline Verheugen
    • , Nadia Schryvers
    • , Gaëlle Varkas
    • , Heleen Cypers
    • , Ruth Wittoek
    • , Yves Piette
    • , Lieve Gyselbrecht
    • , Serge Van Calenbergh
    • , Filip Van den Bosch
    • , Yvan Saeys
    • , Gerald Nabozny
    •  & Dirk Elewaut
  • Article | | open

    Optogenetics is a promising alternative approach for restoration of neuromuscular function. Here the authors establish a closed-loop functional optogenetic stimulation for the control of limb joint angle in murine models, which demonstrates improved control and less fatigue than electrical stimulation systems.

    • Shriya S. Srinivasan
    • , Benjamin E. Maimon
    • , Maurizio Diaz
    • , Hyungeun Song
    •  & Hugh M. Herr
  • Article | | open

    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
    • , Alexander Rosenberg
    • , Javier Rangel-Moreno
    • , Victor Wang
    • , Jason Glanzman
    • , Teresa Owen
    • , Xichao Zhou
    • , Hengwei Zhang
    • , Brendan F. Boyce
    • , Jennifer H. Anolik
    •  & Lianping Xing
  • Article | | open

    Myoblast fusion in skeletal muscle is a complex process but how this is regulated is unclear. Here, the authors identify Ash1L, a histone methyltransferase, as modulating myoblast fusion via activation of the myogenesis gene Cdon, and observe decreased Ash1L expression in Duchenne muscular dystrophy.

    • Ilaria Castiglioni
    • , Roberta Caccia
    • , Jose Manuel Garcia-Manteiga
    • , Giulia Ferri
    • , Giuseppina Caretti
    • , Ivan Molineris
    • , Kenichi Nishioka
    •  & Davide Gabellini
  • Article | | open

    mRNA modifications have been shown to regulate mammalian development and disease. Here the authors show that the m6A methyltransferase Mettl3 ensures translational efficiency of the mesenchymal stem cell lineage allocator Pth1r, promoting osteogenesis and protecting from osteoporosis.

    • Yunshu Wu
    • , Liang Xie
    • , Mengyuan Wang
    • , Qiuchan Xiong
    • , Yuchen Guo
    • , Yu Liang
    • , Jing Li
    • , Rui Sheng
    • , Peng Deng
    • , Yuan Wang
    • , Rixin Zheng
    • , Yizhou Jiang
    • , Ling Ye
    • , Qianming Chen
    • , Xuedong Zhou
    • , Shuibin Lin
    •  & Quan Yuan
  • Article | | open

    Pro-inflammatory factors implicated for the onset of arthritis often have systematic effects, yet arthritis symptoms are mostly limited to the joints. Here the authors show that mechanical strain at the joints promotes the recruitment of monocyte and their differentiation into bone-eroding osteoclast to contribute this tissue specificity.

    • Isabelle Cambré
    • , Djoere Gaublomme
    • , Arne Burssens
    • , Peggy Jacques
    • , Nadia Schryvers
    • , Amélie De Muynck
    • , Leander Meuris
    • , Stijn Lambrecht
    • , Shea Carter
    • , Pieter de Bleser
    • , Yvan Saeys
    • , Luc Van Hoorebeke
    • , George Kollias
    • , Matthias Mack
    • , Paul Simoens
    • , Rik Lories
    • , Nico Callewaert
    • , Georg Schett
    •  & Dirk Elewaut
  • Article | | open

    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
    • , Wenling Li
    • , Ailing Wu
    • , Xu Zhang
    • , Wenxue Tong
    • , Kiwai Kevin Ho
    • , Ling Qin
    • , Hai Song
    •  & Kinglun Kingston Mak
  • Article | | open

    Vascular smooth muscle cell (VSMC) accumulation is associated with cardiovascular disease. Here, the authors combine single-cell RNA sequencing with lineage labelling to profile VSMC heterogeneity in healthy mice. They show that upregulation of Sca1 in a rare VSMC subpopulation marks a cell phenotype that is prevalent in disease.

    • Lina Dobnikar
    • , Annabel L. Taylor
    • , Joel Chappell
    • , Phoebe Oldach
    • , Jennifer L. Harman
    • , Erin Oerton
    • , Elaine Dzierzak
    • , Martin R. Bennett
    • , Mikhail Spivakov
    •  & Helle F. Jørgensen
  • Article | | open

    Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here the authors use ~40 nm cationic nanoparticles to scavenge cfDNA, and demonstrate the potential for nanomedicine to relieve debilitating RA symptoms.

    • Huiyi Liang
    • , Bo Peng
    • , Cong Dong
    • , Lixin Liu
    • , Jiaji Mao
    • , Song Wei
    • , Xinlu Wang
    • , Hanshi Xu
    • , Jun Shen
    • , Hai-Quan Mao
    • , Xiaohu Gao
    • , Kam W. Leong
    •  & Yongming Chen
  • Article | | open

    Approximately 30% of psoriasis patients develop psoriatic arthritis (PsA) and early diagnosis is crucial for the management of PsA. Here, Patrick et al. develop a computational pipeline involving statistical and machine-learning methods that can assess the risk of progression to PsA based on genetic markers.

    • Matthew T. Patrick
    • , Philip E. Stuart
    • , Kalpana Raja
    • , Johann E. Gudjonsson
    • , Trilokraj Tejasvi
    • , Jingjing Yang
    • , Vinod Chandran
    • , Sayantan Das
    • , Kristina Callis-Duffin
    • , Eva Ellinghaus
    • , Charlotta Enerbäck
    • , Tõnu Esko
    • , Andre Franke
    • , Hyun M. Kang
    • , Gerald G. Krueger
    • , Henry W. Lim
    • , Proton Rahman
    • , Cheryl F. Rosen
    • , Stephan Weidinger
    • , Michael Weichenthal
    • , Xiaoquan Wen
    • , John J. Voorhees
    • , Gonçalo R. Abecasis
    • , Dafna D. Gladman
    • , Rajan P. Nair
    • , James T. Elder
    •  & Lam C. Tsoi
  • Article | | open

    The majority of scoliosis is considered idiopathic with onset in adolescence (AIS) and has a genetic contribution. Here, the authors perform an exome wide association study of data from 457 severe AIS cases and 987 controls, and find a missense variant in SLC39A8 is associated with AIS.

    • Gabe Haller
    • , Kevin McCall
    • , Supak Jenkitkasemwong
    • , Brooke Sadler
    • , Lilian Antunes
    • , Momchil Nikolov
    • , Julia Whittle
    • , Zachary Upshaw
    • , Jimann Shin
    • , Erin Baschal
    • , Carlos Cruchaga
    • , Matthew Harms
    • , Cathleen Raggio
    • , Jose A. Morcuende
    • , Philip Giampietro
    • , Nancy H. Miller
    • , Carol Wise
    • , Ryan S. Gray
    • , Lila Solnica-Krezel
    • , Mitchell Knutson
    • , Matthew B. Dobbs
    •  & Christina A. Gurnett
  • Article | | open

    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
    • , Yufan Chen
    • , Eugenia Giannopoulou
    • , Ren Xu
    • , Shiaoching Gong
    • , Matthew B. Greenblatt
    • , Lingegowda S. Mangala
    • , Gabriel Lopez-Berestein
    • , David G. Kirsch
    • , Anil K. Sood
    • , Liang Zhao
    •  & Baohong Zhao
  • Article | | open

    Conventional B cells express clonally specific antigen receptors, but a small subset of B cells from patients and mice with systematic lupus erythematosus simultaneously expresses two distinct antigen receptors. Here the authors show that these dual-specificity B cells have higher levels of MHC-II, depend on IL-21 for expansion, and mount stronger memory response.

    • Allison Sang
    • , Thomas Danhorn
    • , Jacob N. Peterson
    • , Andrew L. Rankin
    • , Brian P. O’Connor
    • , Sonia M. Leach
    • , Raul M. Torres
    •  & Roberta Pelanda
  • Article | | open

    At inflammatory sites, ectopic lymphoid-like structures (ELS) can be induced through the function of chemokine CXCL13 produced by CD4+ T cells. Here the authors show that a transcription factor, Sox4, induces the expression of CXCL13 in CD4 T cells in vitro, and is associated with ELS formation in patients with rheumatoid arthritis.

    • Hiroyuki Yoshitomi
    • , Shio Kobayashi
    • , Aya Miyagawa-Hayashino
    • , Akinori Okahata
    • , Kohei Doi
    • , Kohei Nishitani
    • , Koichi Murata
    • , Hiromu Ito
    • , Tatsuaki Tsuruyama
    • , Hironori Haga
    • , Shuichi Matsuda
    •  & Junya Toguchida
  • Article | | open

    Fibro-adipogenic progenitors (FAPs) resident in skeletal muscle are involved in both regeneration and maladaptive processes. Here, the authors identify subpopulations of FAPs with biological activities implicated in physiological muscle repair that are altered in pathological conditions such as muscular dystrophies.

    • Barbora Malecova
    • , Sole Gatto
    • , Usue Etxaniz
    • , Magda Passafaro
    • , Amy Cortez
    • , Chiara Nicoletti
    • , Lorenzo Giordani
    • , Alessio Torcinaro
    • , Marco De Bardi
    • , Silvio Bicciato
    • , Francesca De Santa
    • , Luca Madaro
    •  & Pier Lorenzo Puri
  • Article | | open

    Muscular dystrophies are characterised by extensive myofibre cell death. Here Morgan et al. show that RIPK3-mediated necroptosis contributes to myofibre cell death in Duchenne muscular dystrophy, and that RIPK3 deletion protects dystrophic mice against myofibre degeneration.

    • Jennifer E. Morgan
    • , Alexandre Prola
    • , Virginie Mariot
    • , Veronica Pini
    • , Jinhong Meng
    • , Christophe Hourde
    • , Julie Dumonceaux
    • , Francesco Conti
    • , Frederic Relaix
    • , Francois-Jerôme Authier
    • , Laurent Tiret
    • , Francesco Muntoni
    •  & Maximilien Bencze
  • Article | | open

    BMP promotes bone formation but its efficacy is limited in some patients. Here, the authors show that osteoporosis patients with a poor response to BMP have increased expression of Smurf1, which targets BMP effectors for degradation, and demonstrate that its chemical inhibition enhances BMP-mediated bone formation in mice.

    • Chao Liang
    • , Songlin Peng
    • , Jie Li
    • , Jun Lu
    • , Daogang Guan
    • , Feng Jiang
    • , Cheng Lu
    • , Fangfei Li
    • , Xiaojuan He
    • , Hailong Zhu
    • , D. W. T. Au
    • , Dazhi Yang
    • , Bao-Ting Zhang
    • , Aiping Lu
    •  & Ge Zhang
  • Article | | open

    Hyperactivation of TGFβ signaling is a common feature of fibrotic diseases. Here the authors show that genetic or pharmacologic inactivation of the tyrosine phosphatase SHP2 prevents TGFβ-induced JAK2/STAT3 signaling, inhibits fibroblast activation and exerts potent anti-fibrotic effects.

    • Ariella Zehender
    • , Jingang Huang
    • , Andrea-Hermina Györfi
    • , Alexandru-Emil Matei
    • , Thuong Trinh-Minh
    • , Xiaohan Xu
    • , Yi-Nan Li
    • , Chih-Wei Chen
    • , Jianping Lin
    • , Clara Dees
    • , Christian Beyer
    • , Kolja Gelse
    • , Zhong-Yin Zhang
    • , Christina Bergmann
    • , Andreas Ramming
    • , Walter Birchmeier
    • , Oliver Distler
    • , Georg Schett
    •  & Jörg H. W. Distler
  • Article | | open

    Endurance and resistance exercise have different effects on skeletal muscle phenotype. Using mouse models and human subjects, the authors show that JNK/Smad2 signaling acts as molecular switch that when activated by resistance exercise leads to hypertrophy, and when inhibited promotes endurance adaptations in muscle.

    • Sarah J. Lessard
    • , Tara L. MacDonald
    • , Prerana Pathak
    • , Myoung Sook Han
    • , Vernon G. Coffey
    • , Johann Edge
    • , Donato A. Rivas
    • , Michael F. Hirshman
    • , Roger J. Davis
    •  & Laurie J. Goodyear
  • Article | | open

    RANKL is a cytokine produced as a membrane-bound and a secreted protein. Here, using mice lacking soluble RANKL, the authors show that the secreted protein is important for osteoclast function, but not for mammary gland and lymphocyte development.

    • Jinhu Xiong
    • , Keisha Cawley
    • , Marilina Piemontese
    • , Yuko Fujiwara
    • , Haibo Zhao
    • , Joseph J. Goellner
    •  & Charles A. O’Brien
  • Article | | open

    Little information is available on molecular changes in response to treatment of rheumatoid arthritis (RA). Here the authors report a multi-omics study collecting patients' transcriptome, proteome, and immunophenotype data to help understand the impact of drug treatments on RA molecular phenotypes.

    • Shinya Tasaki
    • , Katsuya Suzuki
    • , Yoshiaki Kassai
    • , Masaru Takeshita
    • , Atsuko Murota
    • , Yasushi Kondo
    • , Tatsuya Ando
    • , Yusuke Nakayama
    • , Yuumi Okuzono
    • , Maiko Takiguchi
    • , Rina Kurisu
    • , Takahiro Miyazaki
    • , Keiko Yoshimoto
    • , Hidekata Yasuoka
    • , Kunihiro Yamaoka
    • , Rimpei Morita
    • , Akihiko Yoshimura
    • , Hiroyoshi Toyoshiba
    •  & Tsutomu Takeuchi
  • Article | | open

    Adaptor for IL-17 receptors (Act1) is known to be crucial for IL-17-mediated immune responses. Here the authors show that Act1 also functions as a negative regulator of T and B cells by direct inhibition of STAT3.

    • Cun-Jin Zhang
    • , Chenhui Wang
    • , Meiling Jiang
    • , Chunfang Gu
    • , Jianxin Xiao
    • , Xing Chen
    • , Bradley N. Martin
    • , Fangqiang Tang
    • , Erin Yamamoto
    • , Yibo Xian
    • , Han Wang
    • , Fengling Li
    • , R. Balfour Sartor
    • , Howard Smith
    • , M. Elaine Husni
    • , Fu-Dong Shi
    • , Ji Gao
    • , Julie Carman
    • , Ashok Dongre
    • , Susan C. McKarns
    • , Ken Coppieters
    • , Trine N. Jørgensen
    • , Warren J. Leonard
    •  & Xiaoxia Li
  • Article | | open

    Osteocytes reside in a low oxygen environment, but it is not clear if oxygen sensing regulates their function. Here, the authors show that deletion of the oxygen sensor prolyl hydroxylase 2 in osteocytes leads to increased bone mass via regulation of sclerostin, and reduces bone loss in mouse models of osteoporosis.

    • Steve Stegen
    • , Ingrid Stockmans
    • , Karen Moermans
    • , Bernard Thienpont
    • , Patrick H. Maxwell
    • , Peter Carmeliet
    •  & Geert Carmeliet
  • Article | | open

    IFN-γ is central in inflammatory pathogenesis, response to infection and autoimmune diseases. Here the authors show that MMP12 expression is reduced in patients with SLE and that MMP12 post-translationally truncates IFN-y, inhibiting its function and affecting pathogenesis of mouse models of peritonitis, SLE and rheumatoid arthritis.

    • Antoine Dufour
    • , Caroline L. Bellac
    • , Ulrich Eckhard
    • , Nestor Solis
    • , Theo Klein
    • , Reinhild Kappelhoff
    • , Nikolaus Fortelny
    • , Parker Jobin
    • , Jacob Rozmus
    • , Jennifer Mark
    • , Paul Pavlidis
    • , Vincent Dive
    • , Sean J. Barbour
    •  & Christopher M. Overall
  • Article | | open

    Many diseases, such as rheumatoid arthritis, are characterized by a chronic inflammatory state, but it is not clear whether or how this affects the brain. Here, the authors show that the severity of on-going inflammation predicts altered functional brain connectivity in people with rheumatoid arthritis.

    • Andrew Schrepf
    • , Chelsea M. Kaplan
    • , Eric Ichesco
    • , Tony Larkin
    • , Steven E. Harte
    • , Richard E. Harris
    • , Alison D. Murray
    • , Gordon D. Waiter
    • , Daniel J. Clauw
    •  & Neil Basu
  • Article | | open

    Atherosclerosis and osteoporosis are epidemiologically associated, and oxidation specific epitopes (OSEs), which can be neutralized by innate antibodies, are pathogenic for both. Here, the authors show that mice expressing antibody fragments targeted to OSEs are protected from the bone loss induced by high-fat diet and have increased bone mass when fed a normal diet, and that levels of innate antibodies to OSEs decrease with ageing.

    • Elena Ambrogini
    • , Xuchu Que
    • , Shuling Wang
    • , Fumihiro Yamaguchi
    • , Robert S. Weinstein
    • , Sotirios Tsimikas
    • , Stavros C. Manolagas
    • , Joseph L. Witztum
    •  & Robert L. Jilka
  • Article | | open

    Fibroblast-like synoviocytes (FLS) in the intimal layer of the synovium can become invasive and destroy cartilage in patients with rheumatoid arthritis (RA). Here the authors integrate a variety of epigenomic data to map the epigenome of FLS in RA and identify potential therapeutic targets.

    • Rizi Ai
    • , Teresina Laragione
    • , Deepa Hammaker
    • , David L. Boyle
    • , Andre Wildberg
    • , Keisuke Maeshima
    • , Emanuele Palescandolo
    • , Vinod Krishna
    • , David Pocalyko
    • , John W. Whitaker
    • , Yuchen Bai
    • , Sunil Nagpal
    • , Kurtis E. Bachman
    • , Richard I. Ainsworth
    • , Mengchi Wang
    • , Bo Ding
    • , Percio S. Gulko
    • , Wei Wang
    •  & Gary S. Firestein
  • Article | | open

    Ageing is associated with muscle atrophy. Here, the authors show that the secreted glycoprotein Dickkopf 3 promotes muscle atrophy by inducing nuclear import of beta-catenin, its association with FoxO3 and the consequent activation of the atrophy-related genes Atrogin1 and MuRF1.

    • Jie Yin
    • , Lele Yang
    • , Yangli Xie
    • , Yan Liu
    • , Sheng Li
    • , Wenjun Yang
    • , Bo Xu
    • , Hongbin Ji
    • , Lianghua Ding
    • , Kun Wang
    • , Gang Li
    • , Lin Chen
    •  & Ping Hu
  • Article | | open

    Mechanical forces exerted on tendons during locomotion cannot be readily measured without invasive methods. Here, the authors develop a non-invasive wearable device to track tendon loads by measuring shear wave propagation speed, and demonstrate its use during dynamic human movements.

    • Jack A. Martin
    • , Scott C. E. Brandon
    • , Emily M. Keuler
    • , James R. Hermus
    • , Alexander C. Ehlers
    • , Daniel J. Segalman
    • , Matthew S. Allen
    •  & Darryl G. Thelen
  • Article | | open

    CXCR2 antagonism has been shown to be anti-arthritic, but anti-chemokine therapies usually fail in the clinic owing to redundancy in chemokine-receptor interactions. Here the authors develop single-chain antibodies with multiple chemokine specificities to achieve high affinity and broad specificity to mouse and human CXC chemokines with efficacy in a K/BxN serum transfer model of arthritis.

    • Alessandro Angelini
    • , Yoshishige Miyabe
    • , Daniel Newsted
    • , Byron H. Kwan
    • , Chie Miyabe
    • , Ryan L. Kelly
    • , Misha N. Jamy
    • , Andrew D. Luster
    •  & K. Dane Wittrup
  • Article | | open

    Anti-TNF therapy has improved the treatment of inflammatory disease but can predispose to infection and malignancy. Here the authors show an anti-TNF biologic peptide that functionally and selectively targets the TNF-p38 pathway in multiple models of inflammation.

    • Violet R. Mukaro
    • , Alex Quach
    • , Michelle E. Gahan
    • , Bernadette Boog
    • , Zhi H. Huang
    • , Xiuhui Gao
    • , Carol Haddad
    • , Suresh Mahalingam
    • , Charles S. Hii
    •  & Antonio Ferrante
  • Article | | open

    Feingold syndrome is a skeletal dysplasia caused by mutations in MYCN or MIR17HG, but it is not clear if these mutations lead to pathology via a common molecular mechanism. Here, the authors show that mutations in MIR17HG lead to upregulated TGF-β signaling in limb mesenchymal cells, while mutations in MYCN downregulate PI3K signaling.

    • Fatemeh Mirzamohammadi
    • , Anastasia Kozlova
    • , Garyfallia Papaioannou
    • , Elena Paltrinieri
    • , Ugur M. Ayturk
    •  & Tatsuya Kobayashi
  • Article | | open

    The treatment of inflammatory arthritis by local delivery of therapeutics is limited by short half-lives of drugs. Here the authors demonstrate a hydrogel platform that titrates drug release to arthritis activity.

    • Nitin Joshi
    • , Jing Yan
    • , Seth Levy
    • , Sachin Bhagchandani
    • , Kai V. Slaughter
    • , Nicholas E. Sherman
    • , Julian Amirault
    • , Yufeng Wang
    • , Logan Riegel
    • , Xueyin He
    • , Tan Shi Rui
    • , Michael Valic
    • , Praveen K. Vemula
    • , Oscar R. Miranda
    • , Oren Levy
    • , Ellen M. Gravallese
    • , Antonios O. Aliprantis
    • , Joerg Ermann
    •  & Jeffrey M. Karp
  • Article | | open

    Synovial fibroblasts are thought to be central mediators of joint destruction in rheumatoid arthritis (RA). Here the authors use single-cell transcriptomics and flow cytometry to identify synovial fibroblast subsets that are expanded and display distinct tissue distribution and function in patients with RA.

    • Fumitaka Mizoguchi
    • , Kamil Slowikowski
    • , Kevin Wei
    • , Jennifer L. Marshall
    • , Deepak A. Rao
    • , Sook Kyung Chang
    • , Hung N. Nguyen
    • , Erika H. Noss
    • , Jason D. Turner
    • , Brandon E. Earp
    • , Philip E. Blazar
    • , John Wright
    • , Barry P. Simmons
    • , Laura T. Donlin
    • , George D. Kalliolias
    • , Susan M. Goodman
    • , Vivian P. Bykerk
    • , Lionel B. Ivashkiv
    • , James A. Lederer
    • , Nir Hacohen
    • , Peter A. Nigrovic
    • , Andrew Filer
    • , Christopher D. Buckley
    • , Soumya Raychaudhuri
    •  & Michael B. Brenner
  • Article | | open

    The periosteum, a tissue lining the bone surface, and the bone marrow are known to contain bone-forming cells. Here the authors show that skeletal stem cells reside in the mouse periosteum, and that periosteal cells have common embryonic origins with bone marrow stromal/stem cells (BMSCs), but are better at bone repair and long-term integration than BMSCs.

    • Oriane Duchamp de Lageneste
    • , Anaïs Julien
    • , Rana Abou-Khalil
    • , Giulia Frangi
    • , Caroline Carvalho
    • , Nicolas Cagnard
    • , Corinne Cordier
    • , Simon J. Conway
    •  & Céline Colnot
  • Article | | open

    In a lupus environment, basophils accumulate in secondary lymphoid organs where they affect pathogenesis by stimulating autoantibody production. Here the authors show this accumulation is driven by PGD2-induced CXCR4 surface expression and trafficking of basophils.

    • Christophe Pellefigues
    • , Barbara Dema
    • , Yasmine Lamri
    • , Fanny Saidoune
    • , Nathalie Chavarot
    • , Charlotte Lohéac
    • , Emeline Pacreau
    • , Michael Dussiot
    • , Caroline Bidault
    • , Florian Marquet
    • , Mathieu Jablonski
    • , Jonathan M. Chemouny
    • , Fanny Jouan
    • , Antoine Dossier
    • , Marie-Paule Chauveheid
    • , Delphine Gobert
    • , Thomas Papo
    • , Hajime Karasuyama
    • , Karim Sacré
    • , Eric Daugas
    •  & Nicolas Charles
  • Article | | open

    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
    • , Kazuki Nagashima
    • , Takeshi Nitta
    • , Warunee Pluemsakunthai
    • , Chisa Shukunami
    • , Yoichiro Iwakura
    • , Tomoki Nakashima
    • , Kazuo Okamoto
    •  & Hiroshi Takayanagi
  • Article | | open

    The human TNFAIP3 gene, which encodes for A20, is associated with autoimmune diseases. Here, the authors use BAC transgenics combined with CRISPR- and recombineering-mediated genome editing to dissect in vivo and in primary immune cells, the role of enhancers regulating TNFAIP3.

    • Upneet K. Sokhi
    • , Mark P. Liber
    • , Laura Frye
    • , Sungho Park
    • , Kyuho Kang
    • , Tania Pannellini
    • , Baohong Zhao
    • , Rada Norinsky
    • , Lionel B. Ivashkiv
    •  & Shiaoching Gong
  • Article | | open

    TNF is a major therapeutic target for rheumatoid arthritis (RA) and synovial fibroblasts are central to the pathogenesis of RA. Here the authors dissect TNF-induced death and activation signalling in RA synovial fibroblasts and TNF-driven arthritis and indicate that a successful therapeutic strategy might be to target both IKK2 and RIPK3 at the same time.

    • Marietta Armaka
    • , Caroline Ospelt
    • , Manolis Pasparakis
    •  & George Kollias
  • Article | | open

    Th17 cells are a common pathogenic effector cell in autoimmune inflammatory diseases. Here the authors show that the transcription factor RFX1 limits Th17 differentiation and is protective against the pathogenesis of Th17-driven autoimmune diseases.

    • Ming Zhao
    • , Yixin Tan
    • , Qiao Peng
    • , Cancan Huang
    • , Yu Guo
    • , Gongping Liang
    • , Bochen Zhu
    • , Yi Huang
    • , Aiyun Liu
    • , Zijun Wang
    • , Mengying Li
    • , Xiaofei Gao
    • , Ruifang Wu
    • , Haijing Wu
    • , Hai Long
    •  & Qianjin Lu
  • Article | | open

    Heterotopic ossification (HO) is a painful disease of unknown etiology characterized by extraskeletal bone formation after injury. Here the authors show that TGF-β is increased in HO lesions, where it promotes the early stages of HO pathology, and demonstrate that TGF-β inhibition ameliorates HO in mice.

    • Xiao Wang
    • , Fengfeng Li
    • , Liang Xie
    • , Janet Crane
    • , Gehua Zhen
    • , Yuji Mishina
    • , Ruoxian Deng
    • , Bo Gao
    • , Hao Chen
    • , Shen Liu
    • , Ping Yang
    • , Manman Gao
    • , Manli Tu
    • , Yiguo Wang
    • , Mei Wan
    • , Cunyi Fan
    •  & Xu Cao