Musculoskeletal system articles within Nature Communications

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  • Article
    | Open Access

    In their previous study, the researchers systematically revealed that endplate sclerosis is a significant aspect of spine degeneration or aging and a primary source of spinal pain. However, the underlying mechanisms of endplate sclerosis remained unclear. In their current report, it is shown that senescent cells accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging mouse models. The clearance of these senescent cells was found to restrain angiogenesis coupled with endplate sclerosis. Notably, macrophages were identified as undergoing senescence in the sclerotic endplates. The specific knockout of cdkn2a (p16) in macrophages abrogated LSI or aging-induced angiogenesis and sclerosis in the endplates. Moreover, both in vivo and in vitro studies indicated that IL-10 mediates the effects of senescent macrophages on angiogenesis and sclerosis in the endplates. Overall, these findings suggest that senescent macrophages orchestrate angiogenesis coupling with endplate sclerosis via the IL-10/pSTAT3 axis. This study enhances the understanding of the connection between immune senescence and endplate sclerosis and uncovers senescent macrophage-initiated endplate sclerosis as potential therapeutic targets for spinal degeneration.

    • Yonggang Fan
    • , Weixin Zhang
    •  & Shuangfei Ni

  • Article
    | Open Access

    How fast can animals run? Here, the authors show that maximum running speed is limited by different musculoskeletal constraints across animal size: kinetic energy capacity in small animals, and work capacity in large animals.

    • David Labonte
    • , Peter J. Bishop
    •  & Christofer J. Clemente

  • Comment
    | Open Access

    Millions of skeletal remains from South Asia were exported in red markets (the underground economy of human tissues/organs) to educational institutions globally for over a century. It is time to recognize the personhood of the people who were systematically made into anatomical objects and acknowledge the scientific racism in creating and continuing to use them.

    • Sabrina C. Agarwal

  • Article
    | Open Access

    Criteria for evaluating joint articulation in vertebrates are lacking. Here, the authors propose an approach for combining measurements of 3D articular overlap, symmetry, and congruence into a single metric, and apply this to examine the walking stride of Deinonychus antirrhopus.

    • Armita R. Manafzadeh
    • , Stephen M. Gatesy
    •  & Bhart-Anjan S. Bhullar

  • Article
    | Open Access

    There is a strong need for the development of effective and safe disease-modifying osteoarthritis drugs. Here, the authors show that 5-ASA, an anti-inflammatory drug used for ulcerative colitis, shows promise in treating osteoarthritis in mice by improving cartilage and reducing inflammation even when administered at late stages of disease.

    • Jihee Kim
    • , Gina Ryu
    •  & Soo Young Lee

  • Article
    | Open Access

    The 24-hour circadian clocks in cartilage and intervertebral disc play key roles in regulating tissue physiology, yet how they are reset on a daily basis remains elusive. Here the authors show that daily patterns of mechanical loading and associated changes in osmolarity provide a tissue-type specific entrainment time cue for these skeletal clocks.

    • Michal Dudek
    • , Dharshika R. J. Pathiranage
    •  & Qing-Jun Meng

  • Article
    | Open Access

    Skeletal muscle’s metabolic status has an impact on health and the prognosis of chronic diseases. Here the authors unveil an atlas of open chromatin regions in skeletal muscles using single-nucleus techniques on juvenile male mice, highlight regulatory dynamics between normal and denervated states, and pinpoint ELK4 as a pivotal factor in muscle atrophy.

    • Hongchun Lin
    • , Hui Peng
    •  & Zhaoyong Hu

  • Article
    | Open Access

    Here the authors report new human fossils from Tam Pà Ling cave, Laos, consisting of a cranial and a tibial fragment, dated to 68–86 thousand years ago. This find confirms that Homo sapiens were present in Southeast Asia by this time and the shape of the fossils indicates they may have descended from non-local populations.

    • Sarah E. Freidline
    • , Kira E. Westaway
    •  & Fabrice Demeter

  • Article
    | Open Access

    Here, the authors provide an exome study of hand grip strength, a proxy of generalized muscle strength. They identify six exome-wide significant genes, with links to disease, and additivity of rare and common genetic variant effects on muscle strength.

    • Yunfeng Huang
    • , Dora Bodnar
    •  & Heiko Runz

  • Article
    | Open Access

    The mechanisms that drive myocyte orientation and fusion to control muscle directionality are not well understood. Here authors show that the developing skeleton produces mechanical tension that instructs the directional outgrowth of skeletal muscles.

    • Kazunori Sunadome
    • , Alek G. Erickson
    •  & Igor Adameyko

  • Article
    | Open Access

    cAMP is an important second messenger involved in many aspects of biological processes. Here, Li et al. shows that blood vessel epicardial substance (BVES) is a negative regulator of cAMP signaling required for maintaining muscle mass and function.

    • Haiwen Li
    • , Peipei Wang
    •  & Renzhi Han

  • Article
    | Open Access

    Some forms of mitochondrial dysfunction can cause sterile inflammation, but the way in which it might affect muscle fitness is not well understood. Here, the authors show that altered mitochondrial dynamics can cause the production of mitochondrial DNA-driven inflammatory signals mediated by endosome-mitochondria contacts, leading to muscle inflammation, atrophy, reduced physical performance and enhanced exercise-induced inflammatory responses.

    • Andrea Irazoki
    • , Isabel Gordaliza-Alaguero
    •  & Antonio Zorzano

  • Article
    | Open Access

    The group of Shih-Yin Tsai observed age-associated neuromuscular junction structural instability in male but not female mice which is driven by dysregulation of mTOR complex 1 activity. Genetic activation of the downstream phosphorylation target 4EBP1 in the muscle remodeled the neuromuscular junction and enhanced synaptic transmission.

    • Seok-Ting J. Ang
    • , Elisa M. Crombie
    •  & Shih-Yin Tsai

  • Article
    | Open Access

    Ji and colleagues identify Sirt6 as a regulator of chondrocyte senescence. Mechanistically, Sirt6 physically interacts with STAT5 and deacetylates it at K163, which reduces the IL-15/JAK3-induced STAT5 translocation from cytoplasm to nucleus.

    • Ming-liang Ji
    • , Hua Jiang
    •  & Jun Lu

  • Article
    | Open Access

    Myoblast fusion is essential for development of multinucleated myofibers. Here, the authors show that ablation of Elmo 1 and Elmo2 impairs myoblast fusion in mice, and that expression of an open conformation of Elmo2 promotes muscle regeneration and improves the phenotype of Dysferlin-null dystrophic mice.

    • Viviane Tran
    • , Sarah Nahlé
    •  & Jean-François Côté

  • Article
    | Open Access

    The authors present cryogenic contrast-enhanced MicroCT (cryo-CECT), which by freezing stained samples at optimal freezing rates improves the visualization of the tissue microstructure. They demonstrate quantitative 3D analysis of individual tissue constituents, such as muscle and collagen fibers.

    • Arne Maes
    • , Camille Pestiaux
    •  & Greet Kerckhofs

  • Article
    | Open Access

    How different physical configurations between sarcomeres and mitochondria alter energetic support for contractile function of skeletal muscle is not clear. Here the authors use advanced 3D imaging and analysis techniques to show how space is made for mitochondria within the tightly packed sarcomere networks of striated muscle cells.

    • Prasanna Katti
    • , Alexander S. Hall
    •  & Brian Glancy

  • Article
    | Open Access

    Osteocytes play an important role in the development and progression of tumour-associated bone disease. Here the authors report an interaction between malignant plasma cells and osteocytes in multiple myeloma and show that the osteocyte-expressed major histocompatibility complex class II transactivator (CIITA) contributes to myeloma-induced bone lesions.

    • Huan Liu
    • , Jin He
    •  & Jing Yang

  • Article
    | Open Access

    Boyer et al. created genetic mouse models of muscular dystrophy in which satellite cells were selectively depleted. The depletion of satellite cells at select times was protective. Myofibers no longer had plasma membrane instability leading to tissue wasting in the muscular dystrophies.

    • Justin G. Boyer
    • , Jiuzhou Huo
    •  & Jeffery D. Molkentin

  • Article
    | Open Access

    Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, the authors show that an RET-induced increase in PGC-1α4 expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions.

    • Jin-Ho Koh
    • , Mark W. Pataky
    •  & K. Sreekumaran Nair

  • Article
    | Open Access

    Exercise is helpful to counteract obesity and the related complications, and positive effects are associated to a switch of muscle fibres to an oxidative type. Here, the authors show that sirtuin 6 overexpression in mice induces such a switch by modulating Sox6 and CREB signalling, suggesting that sirtuin 6 may be a target for exercise mimetics.

    • Mi-Young Song
    • , Chang Yeob Han
    •  & Byung-Hyun Park

  • Article
    | Open Access

    Endoplasmic Reticulum stress induces cell non-autonomous Unfolded Protein Response (UPR) activation. Here the authors show that long-chain ceramides are secreted from muscle cells in extracellular vesicles and induce cell non-autonomous UPR activation in muscle cells in response to lipotoxcity.

    • Ben D. McNally
    • , Dean F. Ashley
    •  & Lee D. Roberts

  • Article
    | Open Access

    Bone remodeling involves a switch between bone formation and resorption, but the mechanisms is unclear. Here, the authors show that intercellular communication via extracellular vesicles secreted by mature osteoblasts is a key factor for the switching, via a microRNA-mediated mechanism.

    • Maki Uenaka
    • , Erika Yamashita
    •  & Masaru Ishii

  • Article
    | Open Access

    Polymyositis (PM) is a chronic inflammatory myopathy characterized by progressive muscle weakness. Here the authors showed that muscle fibers in PM undergo necroptosis and aggravate inflammation via releasing pro-inflammatory molecules such as HMGB1.

    • Mari Kamiya
    • , Fumitaka Mizoguchi
    •  & Shinsuke Yasuda

  • Article
    | Open Access

    Mechanical force is critical for the development and remodeling of bones. Here the authors report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine via regulating the expression of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 in osteoblasts.

    • Ziang Xie
    • , Lei Hou
    •  & Shunwu Fan

  • Article
    | Open Access

    Muscle undergoes hypertrophy and atrophy in response to physiological stimuli or in pathological conditions, which is partially controlled through altered gene expression. Here the authors report that m6A methyltransferase METTL3 and mRNA m6A post-transcriptional modifications as a mechanism that regulates muscle hypertrophy and atrophy via myostatin signalling in mice.

    • Jennifer M. Petrosino
    • , Scott A. Hinger
    •  & Federica Accornero

  • Article
    | Open Access

    Current treatments cannot significantly alleviate the radiographic progression in ankylosing spondylitis (AS), which results in joints stiffness and bony fusion of AS. Smo inhibitor sonidegib retards the pathological new bone formation in AS through targeting dysfunctional chondrogenesis.

    • Fenli Shao
    • , Qianqian Liu
    •  & Yang Sun

  • Article
    | Open Access

    Dual-energy X-ray absorptiometry and the Fracture Risk Assessment Tool are recommended tools for osteoporotic fracture risk evaluation, but are underutilized. Here, the authors present an opportunistic tool to identify fractures, predict bone mineral density and evaluate fracture risk using plain pelvis and lumbar spine radiographs.

    • Chen-I Hsieh
    • , Kang Zheng
    •  & Chang-Fu Kuo

  • Article
    | Open Access

    Soft tissue trauma can result in aberrant osteochondral differentiation of local mesenchymal progenitor cells. Here the authors show that, in mice, soft tissue trauma results in NGF expression by perivascular cells, which leads to axonal invasion and drives abnormal osteochondral differentiation, and show that this process can be prevented by inhibition of NGF signaling.

    • Seungyong Lee
    • , Charles Hwang
    •  & Benjamin Levi

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