Metabolic bone disease articles within Nature Communications

Featured

• Article
  12 February 2024 | Open Access

  Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src

  The authors of this manuscript identify that Gpr54 activation by its natural ligand Kisspeptin-10 can abrogate bone resorption. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase, which causes Dusp18 to dephosphorylate Src at Tyr 416.

  • Zhenxi Li
  • , Xinghai Yang
  •  & Jianru Xiao

• Article
  30 January 2024 | Open Access

  Rescuing SERCA2 pump deficiency improves bone mechano-responsiveness in type 2 diabetes by shaping osteocyte calcium dynamics

  Here, Shao et. al attribute the reduction in bone mechano-responsiveness seen in type 2 diabetes to abnormal osteocytic calcium dynamics. They identify reduced SERCA2 pump activity as a mediator of this process and show that rescuing SERCA2 significantly improves bone mechanical adaptation in this context.

  • Xi Shao
  • , Yulan Tian
  •  & Da Jing

• Article
  07 December 2023 | Open Access

  Functional and analytical recapitulation of osteoclast biology on demineralized bone paper

  Here, authors report demineralized bone paper-based in vitro osteogenic culture and assay platforms that replicate essential bone tissue complexity, osteoclast processes, and drug responses with high fidelity and predictive power.

  • Yongkuk Park
  • , Tadatoshi Sato
  •  & Jungwoo Lee

• Article
  27 October 2023 | Open Access

  Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways

  Gut microbiota has been reported to influence osteoporosis risk, but the individual species, and underlying mechanisms, remain largely unknown. Here, the authors identify Bacteroides vulgatus and serum valeric acid as potential targets for osteoporosis prevention/treatment.

  • Xu Lin
  • , Hong-Mei Xiao
  •  & Hong-Wen Deng

• Article
  20 June 2023 | Open Access

  UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis

  The authors identify UBAP2 as a novel osteoporosis susceptibility gene by performing association studies focusing on coding regions of the genome, and report that it plays a role in bone homeostasis through the regulation of bone remodelling.

  • Jeonghyun Kim
  • , Bo-Young Kim
  •  & Seon-Yong Jeong

• Article
  20 April 2023 | Open Access

  Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study

  Here, the authors employ data from the population-based Norwegian HUNT cohort (n = 5196, including women and men) to associate the presence of three gut microbial species – Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum – with higher lean mass.

  • Louise Grahnemo
  • , Maria Nethander
  •  & Claes Ohlsson

• Article
  25 February 2023 | Open Access

  Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice

  Gonadotropes in the pituitary secrete follicle-stimulating hormone and luteinizing hormone to control gonadal function and fertility, but whether they exert actions on extra-gonadal organs is not fully understood. Here the authors report that gonadotropes regulate liver steatosis independent of the ovaries in mice.

  • Sen Qiao
  • , Samer Alasmi
  •  & Ulrich Boehm

• Article
  21 February 2023 | Open Access

  Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts

  Despite the importance of osteoclast secretory lysosomes in bone digestion, the proteins that regulate them remain ill defined. Here, the authors identify Slc37a2 as a secretory lysosome sugar transporter that is required for maintenance of skeletal bone mass.

  • Pei Ying Ng
  • , Amy B. P. Ribet
  •  & Nathan J. Pavlos

• Article
  18 January 2023 | Open Access

  Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure

  Otosclerosis is a common form of hearing loss, with an unclear genetic etiology. Here, the authors perform a genome-wide association study meta-analysis of otosclerosis identifying 27 genetic loci, pointing to genes involved in bone remodeling, skeletal disorders and transforming growth factor β signaling.

  • Joel T. Rämö
  • , Tuomo Kiiskinen
  •  & Aarno Palotie

• Article
  11 January 2023 | Open Access

  TGFβ1⁺CCR5⁺ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice

  Age-related osteoporosis is known to be dependent on TGFβ1 signalling. Here the authors show that a subset of neutrophils (identified by TGFβ1⁺CCR5⁺) increase during aging in mouse bone marrow resulting in bone loss, while a CCR5 antagonist can reduce the neutrophil numbers and increase bone mass in aged mice.

  • Jinbo Li
  • , Zhenqiang Yao
  •  & Brendan F. Boyce

• Article
  19 October 2022 | Open Access

  Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery

  Fibrodysplasia ossificans progressiva is an ultra-rare genetic disorder with progressive heterotopic ossification. Yang et al develop different gene therapy approaches and show their efficacy in mouse models and in human induced pluripotent stem cells.

  • Yeon-Suk Yang
  • , Jung-Min Kim
  •  & Jae-Hyuck Shim

• Article
  16 August 2022 | Open Access

  A TrkB agonist prodrug prevents bone loss via inhibiting asparagine endopeptidase and increasing osteoprotegerin

  BDNS and TrkB are involved in bone fracture healing by inhibiting AEP. Here the authors show that a TrkB agonist prodrug can inhibit AEP and promote bone formation in osteoporotic mice.

  • Jing Xiong
  • , Jianming Liao
  •  & Keqiang Ye

• Article
  16 August 2022 | Open Access

  A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

  Identification of senescent cells in vivo remains a challenging task. Here the authors present and validate a senescence gene set called SenMayo enriched in human and murine aged tissues.

  • Dominik Saul
  • , Robyn Laura Kosinsky
  •  & Sundeep Khosla

• Article
  18 March 2022 | Open Access

  Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox

  This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.

  • Zhen-Xing Wang
  • , Zhong-Wei Luo
  •  & Hui Xie

• Article
  10 January 2022 | Open Access

  Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

  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
  01 November 2021 | Open Access

  Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin

  The molecular circuitry that drives dendrite formation during osteocytogenesis remains poorly understood. Here the authors show that deletion of Sp7, a gene linked to rare and common skeletal disease, in mature osteoblasts and osteocytes causes severe defects in osteocyte dendrites.

  • Jialiang S. Wang
  • , Tushar Kamath
  •  & Marc N. Wein

• Article
  16 September 2021 | Open Access

  Automated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning

  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
  03 June 2021 | Open Access

  A functional motif of long noncoding RNA Nron against osteoporosis

  LncRNAs are implicated in the pathogenesis of a number of diseases. Here, the authors show that the lncRNA Nron suppresses bone resorption, and show that delivery of a functional motif of Nron increases bone mass in mouse models of osteoporosis.

  • Fujun Jin
  • , Junhui Li
  •  & Xiaogang Wang

• Article
  23 April 2021 | Open Access

  RANKL regulates male reproductive function

  There are few treatments for male infertility. Here, the authors show that the receptor activator of NF-κB ligand (RANKL) signalling pathway has important functions in sperm production and maturation, improves fertility in male mice and shows potential as a male infertility target.

  • Martin Blomberg Jensen
  • , Christine Hjorth Andreassen
  •  & Anders Juul

• Article
  24 January 2020 | Open Access

  PTH 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

• Article
  23 January 2020 | Open Access

  Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis

  An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

  • Rong Fu
  • , Wen-Cong Lv
  •  & Zhao-Qiu Wu

• Article
  07 January 2020 | Open Access

  Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

  Anti-resorptive bone therapies also inhibit bone formation, as osteoclasts secrete factors that stimulate bone formation by osteoblasts. Here, the authors identify osteoclast-secreted factors that couple bone resorption to bone formation in healthy subjects, and show that osteoclast-derived DPP4 may be a factor coupling bone resorption to energy metabolism.

  • Megan M. Weivoda
  • , Chee Kian Chew
  •  & Sundeep Khosla

• Article
  04 July 2019 | Open Access

  Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis

  The adaptor protein SHN3 suppresses new bone formation by controlling osteoblast activity. Here, the authors show that ablation of SHN3 function, either genetically or by delivering an artificial miRNA via AAV9, rescues bone loss in osteoporotic mice, and show that engineering of the AAV9 capsid improves targeting to bone

  • Yeon-Suk Yang
  • , Jun Xie
  •  & Jae-Hyuck Shim

• Article
  26 June 2019 | Open Access

  TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis

  Increased inflammation during ageing promotes osteoporosis by activating osteoclast function and inhibiting osteoblasts. Here, the authors show that TGFβ1 release from bone matrix during ageing induces degradation of TRAF3 in mesenchymal progenitor cells, leading to reduced osteoblast differentiation and increased osteoclast formation, and suggesting that pharmacological stabilization of TRAF3 could ameliorate age-related osteoporosis.

  • Jinbo Li
  • , Akram Ayoub
  •  & Brendan F. Boyce

• Article
  08 April 2019 | Open Access

  TMCO1-mediated Ca²⁺ leak underlies osteoblast functions via CaMKII signaling

  TMCO1 is a recently described endoplasmic reticular Ca²⁺ channel. Here, the authors show it is important for osteoblast function and bone formation in mice, and identify a novel pathway linking local increases in Ca²⁺ at the ER surface with the posttranslational modification of RUNX2.

  • Jianwei Li
  • , Caizhi Liu
  •  & Yingxian Li

• Article
  22 March 2019 | Open Access

  TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone

  Parathyroid hormone (PTH) is used to treat osteoporosis, but its therapeutic mechanism remains unclear. Here, the authors show that Tgif1 is a PTH target gene, and that its deletion impairs the function of osteoblasts and PTH-induced bone formation in mice.

  • Hiroaki Saito
  • , Andreas Gasser
  •  & Eric Hesse

• Article
  19 March 2019 | Open Access

  Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density

  GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.

  • Alessandra Chesi
  • , Yadav Wagley
  •  & Struan F. A. Grant

• Article
  11 January 2019 | Open Access

  Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones

  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
  •  & Holly A. Ingraham

• Article
  14 November 2018 | Open Access

  Mettl3-mediated m⁶A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis

  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
  •  & Quan Yuan

• Article
  05 October 2018 | Open Access

  Bone 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

• Article
  24 August 2018 | Open Access

  Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis

  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
  •  & Ge Zhang

• Article
  02 July 2018 | Open Access

  Osteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin

  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
  •  & Geert Carmeliet

• Article
  06 June 2018 | Open Access

  Oxidation-specific epitopes restrain bone formation

  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
  •  & Robert L. Jilka

• Article
  20 December 2017 | Open Access

  The HIV co-receptor CCR5 regulates osteoclast function

  CCR5 is a co-receptor for HIV, and loss of function is associated with lower incidence of HIV but also with bone-destructive diseases. Here the authors show that ablation of CCR5 impairs osteoclast function and improves resistance to osteoporosis in mouse models.

  • Ji-Won Lee
  • , Akiyoshi Hoshino
  •  & Tadahiro Iimura

• Article
  03 November 2017 | Open Access

  Programmed cell senescence in skeleton during late puberty

  Mesenchymal stem cells are essential for bone development, but it is unclear if their activity is maintained after late puberty, when bone growth decelerates. The authors show that during late puberty in mice, these cells undergo senescence under the epigenetic control of Ezh2.

  • Changjun Li
  • , Yu Chai
  •  & Mei Wan

• Article
  20 February 2017 | Open Access

  SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts

  The balance between osteoclast and osteoblast-mediated bone turnover is essential for bone health and homeostasis. Here the authors show that both germline and osteoblast-specificSmurf2-deficient mice have osteoporosis as a result of increased osteoblast RANKL production and excess osteoclastogenesis.

  • Zhan Xu
  • , Matthew B. Greenblatt
  •  & Weiguo Zou

• Article
  19 January 2017 | Open Access

  Gα13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3β-NFATc1 signalling pathway

  Osteoclasts are bone resorptive cells and an attractive target to treat diseases characterized by excessive bone loss, but little is known about osteoclast inhibition. Here the authors identify Gα13 as an intracellular inhibitor of osteoclastogenesis that can prevent bone loss in mice via Akt activation and inhibition of RhoA signalling.

  • Mengrui Wu
  • , Wei Chen
  •  & Yi-Ping Li

• Article
  18 November 2016 | Open Access

  Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism

  Hypoparathyroidism and osteoporosis can be treated with parathyroid hormone, but frequent injections are required. Here the authors develop a small-molecule agonist for the parathyroid hormone type I receptor that can be administered orally, and demonstrate its efficacy in rats.

  • Tatsuya Tamura
  • , Hiroshi Noda
  •  & Yoshiki Kawabe

• Article
  19 October 2016 | Open Access

  SIKs control osteocyte responses to parathyroid hormone

  Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.

  • Marc N. Wein
  • , Yanke Liang
  •  & Henry M. Kronenberg

• Article
  22 September 2016 | Open Access

  GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation

  GDF11 is related to myostatin yet has no known role in postnatal bone turnover. Here the authors show that recombinant GDF11 injection causes bone loss and impairs healing by driving osteoclastogenesis while inhibiting osteoblast differentiation, plus they show that anti-GDF11 Ab can inhibit bone loss in ovariectomy and ageing mouse models.

  • Weiqing Liu
  • , Liyan Zhou
  •  & Quan Yuan

• Article
  06 January 2016 | Open Access

  Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures

  Bone mineral density (BMD) is the best predictor of osteoporotic fracture risk. Here, the authors perform a genome wide association study in Icelanders and people of European and East-Asian descent, and identify a new allele in intron 15 of the PTCH1gene that associates with reduced BMD.

  • Unnur Styrkarsdottir
  • , Gudmar Thorleifsson
  •  & Kari Stefansson

• Article
  17 June 2015 | Open Access

  NELL-1 in the treatment of osteoporotic bone loss

  The growth factor NELL-1 induces bone formation during development, but its role in osteoporosis is unknown. This study shows that NELL-1 binding to integrin ß1 induces Wnt/ß-catenin signalling in the bone and restores bone mineral density in osteoporotic mice and sheep, suggesting the therapeutic potential of NELL-1 for the treatment of bone loss.

  • Aaron W. James
  • , Jia Shen
  •  & Chia Soo

• Article | 03 February 2015

  Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation

  Small-molecule C21 inhibits Rac GTPase activation by Dock5, which decreases osteoclast activity in vitro. Using three mouse models where bone loss is caused by hyperactive osteoclasts, Vives et al. show that C21 treatment safely and efficiently prevents osteoporosis while preserving bone formation.

  • Virginie Vives
  • , Gaëlle Cres
  •  & Anne Blangy

• Article | 11 February 2014

  A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods

  Allosteric sites are an increasingly used target for drug design. Here, the authors computationally predict an allosteric site in cathepsin K and subsequently identify a small-molecule allosteric modifier.

  • Marko Novinec
  • , Matevž Korenč
  •  & Antonio Baici