Musculoskeletal abnormalities articles within Nature Communications

Featured

• Article
  25 November 2021 | Open Access

  STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis

  Autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES) is associated with mutations in STAT3, and clinical manifestations include skeletal deformities. Here, the authors show that inactivation of STAT3 in osteoblast induces AD-HIES-like skeletal defects by impairing osteogenesis, and show that pharmacological STAT3 activation rescues the phenotype.

  • Siru Zhou
  • , Qinggang Dai
  •  & Lingyong Jiang

• Article
  23 June 2020 | Open Access

  Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

  Mutations in human PIEZO2, encoding for a mechanosensitive ion channel, lead to skeletal abnormalities including scoliosis and hip dysplasia. Here, the authors show that deletion of Piezo2 in proprioceptive neurons, but not in skeletal lineages, recapitulated the human phenotype in mice.

  • Eran Assaraf
  • , Ronen Blecher
  •  & Elazar Zelzer

• Article
  10 April 2018 | Open Access

  Distinct molecular pathways mediate Mycn and Myc-regulated miR-17-92 microRNA action in Feingold syndrome mouse models

  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
  •  & Tatsuya Kobayashi

• Article
  06 July 2016 | Open Access

  MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

  Osteogenesis imperfecta (OI) is genetically linked to autosomal dominant or autosomal recessive mutations. Here, Marini et al. describe two families with X-chromosome-linked OI with mutations in MBTPS2 that alter regulated intramembrane proteolysis and subsequent defects in collagen crosslinking and osteoblast function.

  • Uschi Lindert
  • , Wayne A. Cabral
  •  & Vorasuk Shotelersuk

• Article
  03 May 2016 | Open Access

  Laminin regulates PDGFRβ⁺ cell stemness and muscle development

  Muscle PDGFRβ⁺ cells are interstitial stem/progenitor cells with myogenic potential. Here, Yao et al. show that PDGFRβ⁺cell-derived laminin actively regulates their proliferation, differentiation and fate determination.

  • Yao Yao
  • , Erin H. Norris
  •  & Sidney Strickland

• Article
  11 April 2016 | Open Access

  Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy

  Patients with myotonic dystrophy (MD) suffer from severe cardiac issues of unknown aetiology. Freyermuth et al. show that fatal changes in cardiac electrophysiological properties in humans and mice with MD may arise from misregulation of the alternative splicing of the cardiac Na⁺ channel SCN5Atranscript, resulting in expression of its fetal form.

  • Fernande Freyermuth
  • , Frédérique Rau
  •  & Nicolas Charlet-Berguerand

• Article
  21 March 2016 | Open Access

  Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation

  Primary cilia are highly conserved microtubule-based organelles that play essential roles in several cellular processes including osteogenesis. Here the authors show that intraflagellar protein IFT80 regulates osteoblast differentiation by balancing signalling though the canonical and non-canonical Hedgehog pathways.

  • Xue Yuan
  • , Jay Cao
  •  & Shuying Yang

• Article
  11 March 2016 | Open Access

  Hexose enhances oligonucleotide delivery and exon skipping in dystrophin-deficient mdx mice

  Exon-skipping therapies such as systemic i.v. administration of morpholino are being explored as a means of treating Duchenne muscular dystrophy. Here the authors show that adding a glucose-fructose mix can enhance uptake of phosphorodiamidate morpholino oligomer and its therapeutic effect in mdxmice.

  • Gang Han
  • , Ben Gu
  •  & HaiFang Yin

• Article
  08 February 2016 | Open Access

  Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia

  Craniofacial microsomia is a congenital anomaly that affects the development of the skull. Here, the authors perform a genome-wide association study on patients in China and identify particular loci that provide insights into genetic mechanisms.

  • Yong-Biao Zhang
  • , Jintian Hu
  •  & Qingguo Zhang

• Article
  21 January 2016 | Open Access

  Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation

  The TCOF1 gene is mutated in Treacher Collin's syndrome, a congenital craniofacial syndrome. Here, the authors show that Tcof1loss-of-function results in oxidative stress induced DNA damage and neuroepithelial cell death, and addition of antioxidants to pregnant mutant mice protected against these defects.

  • Daisuke Sakai
  • , Jill Dixon
  •  & Paul A. Trainor

• Article
  14 January 2016 | Open Access

  Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects

  A challenge in regenerative medicine is the development of cell-free, non-immunogenic miRNA-delivering scaffolds. Here the authors design a cell-free scaffold capable of efficient and prolonged delivery of miRNA-26a to endogenous cells and show that it can regenerate a full-thickness calvarial bone defect in mice.

  • Xiaojin Zhang
  • , Yan Li
  •  & Peter X. Ma

• Article
  27 October 2015 | Open Access

  Numb is required to prevent p53-dependent senescence following skeletal muscle injury

  Regeneration of skeletal muscle relies on the function of muscle satellite cells. Here, Le Roux et al. show that the endocytic adaptor protein Numb promotes skeletal muscle regeneration after injury by preventing a p53-dependent senescence of satellite cells and consequent inflammation and fibrosis.

  • Isabelle Le Roux
  • , Julie Konge
  •  & Shahragim Tajbakhsh

• Article
  08 October 2015 | Open Access

  Detyrosinated microtubules modulate mechanotransduction in heart and skeletal muscle

  Microtubules are transducers of mechanical energy in muscle cells. Here, the authors show that mechanotransduction is regulated by post-translational detyrosination of microtubules in mouse heart and skeletal muscle, and that reducing detyrosination ameliorates symptoms in a model of Duchenne muscular dystrophy.

  • Jaclyn P. Kerr
  • , Patrick Robison
  •  & Christopher W. Ward

• Article | 22 September 2015

  Role of T-cell reconstitution in HIV-1 antiretroviral therapy-induced bone loss

  HIV infection causes significant bone loss, which is worsened by antiretroviral therapy (ART). Here, the authors use a mouse model to show that T cell repopulation and/or immune reactivation after ART leads to complex inflammatory effects driving bone turnover and bone loss.

  • Ighovwerha Ofotokun
  • , Kehmia Titanji
  •  & M. Neale Weitzmann

• Article
  07 July 2015 | Open Access

  Kindlin-2 controls TGF-β signalling and Sox9 expression to regulate chondrogenesis

  The Kidlins are proteins found in cell focal adhesion sites where they regulate integrins, and in the nucleus where their role is unknown. Here the authors show that Kindlin-2 controls chondrogenesis by regulating integrin b1 activation and Sox9 and TGF-β nuclear signalling.

  • Chuanyue Wu
  • , Hongli Jiao
  •  & Guozhi Xiao

• Article | 07 July 2015

  MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

  Skeletal muscle stem cells (satellite cells) express different levels of a critical transcriptional regulator Pax7. Here, the authors show that miR-431 regulates Pax7 levels in satellite cells of the developing and regenerating muscle, and that increased miR-431expression in these cells alleviates symptoms of muscular dystrophy in mice.

  • Rimao Wu
  • , Hu Li
  •  & Dahai Zhu

• Article | 13 April 2015

  G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

  In response to injury, satellite cells (SCs) asymmetrically divide to self-renew and repair muscle. Here the authors show that a cytokine G-CSF is crucial for long-term expansion of activated SCs and muscle regeneration in mice, suggesting that G-CSF treatment may have beneficial effect in Duchenne muscular dystrophy.

  • Nozomi Hayashiji
  • , Shinsuke Yuasa
  •  & Keiichi Fukuda

• Article
  10 April 2015 | Open Access

  MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease

  Collagen 3 is increased during tendon repair, but is then replaced by Collagen 1 that has superior biomechanical properties. Here the authors show that IL-33 is induced by tendon damage and regulates miR-29a, which controls Collagen 3 production and feeds back on IL-33, orchestrating tendon repair.

  • Neal L. Millar
  • , Derek S. Gilchrist
  •  & Iain B. McInnes

• Article
  10 April 2015 | Open Access

  Regulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy

  FoxO transcription factors promote muscle atrophy in response to stresses such as low nutrient availability. By generating muscle-specific FoxO triple-knockout mice, Milan et al.identify mechanisms by which the FoxO transcriptional network coordinates autophagic and proteasomal protein degradation.

  • Giulia Milan
  • , Vanina Romanello
  •  & Marco Sandri

• Article
  18 March 2015 | Open Access

  A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females

  Girls are tenfold more likely than boys to require surgical treatment for idiopathic scoliosis, a common paediatric skeletal disorder. Here, Sharma et al. identify the first sexually dimorphic idiopathic scoliosis risk locus, and demonstrate that it may play a role in the regulation of spinal cells.

  • Swarkar Sharma
  • , Douglas Londono
  •  & Carol A. Wise

• Article
  03 September 2014 | Open Access

  ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease

  Scoliosis is a complex genetic disorder characterized by spinal curvature. Here, the authors present experimental zebrafish models of idiopathic and congenital scoliosis and suggest a role for dysregulated Wnt activity in scoliosis aetiology.

  • Madeline Hayes
  • , Xiaochong Gao
  •  & Brian Ciruna

• Article | 28 June 2013

  Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules

  Myotonic dystrophy type 1 (DM1) is caused by defects in the alternative splicing of pre-mRNA. Childs-Disney and colleagues report two small molecules that either induce or reverse DM1-associated splicing defects by modulating the binding of pre-mRNA to muscleblind-like 1 protein.

  • Jessica L. Childs-Disney
  • , Ewa Stepniak-Konieczna
  •  & Matthew D. Disney

• Article | 04 June 2013

  Stac3 is a component of the excitation–contraction coupling machinery and mutated in Native American myopathy

  Skeletal muscle contractions are regulated by a process known as excitation–contraction coupling (ECC), defects in which can cause myopathies. Here Horstick et al.show that the protein STAC3 is a component of the ECC machinery and identify mutations in STAC3 as the cause of Native American Myopathy.

  • Eric J. Horstick
  • , Jeremy W. Linsley
  •  & John Y. Kuwada