Evidence map›Paper›PMID 35244027›Full record

ArticleeLife2022

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling.

Kai Sun, Chun Wang, Jianqiu Xiao, Michael D Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer and 3 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Activation of the noncanonical inflammasome-GSDMD pathway triggers pyroptosis in bone marrow and promotes periosteal bone formation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. International journal of molecular sciences · 2024
    Article
  8. Review
  9. Article
  10. Pyroptosis in health and disease.American journal of physiology. Cell physiology · 2024
    Review
  11. Article
  12. Review
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Kai SunXi'an Jiaotong University Health Science Center, Xi'an, China.
Chun WangDivision of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, United States.
Jianqiu XiaoDivision of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, United States.
Michael D BrodtDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, United States.
Luorongxin YuanDivision of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, United States.
Tong YangXi'an Jiaotong University Health Science Center, Xi'an, China.
Yael AlippeDivision of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, United States.
Huimin HuDepartment of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Dingjun HaoXi'an Jiaotong University Health Science Center, Xi'an, China.
Yousef Abu-AmerDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, United States.ORCID 0000-0002-5890-5086
Matthew J SilvaDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, United States.
Jie ShenDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, United States.
Gabriel MbalavieleDivision of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, United States.ORCID 0000-0003-4660-0952
Xi'an Honghui Hospital · CNShriners Hospitals for Children - Erie · US

Funding

Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI MATTHEW J SILVA · 2019 to 2026
$6.8M
OSTEOGENIC AND ANGIOGENIC RESPONSE TO SKELETAL LOADINGR01AR050211 · NIAMS · WASHINGTON UNIVERSITY · PI SILVA, MATTHEW J · 2003 to 2020
$5.0M
Regulatory Mechanisms of Implant-Induced OsteolysisR01AR049192 · NIAMS · WASHINGTON UNIVERSITY · PI ABU-AMER, YOUSEF · 2004 to 2019
$4.3M
Differential Inflammasome Regulation in the pathogenesis of S. aureus osteomyelitisR01AI161022 · NIAID · WASHINGTON UNIVERSITY · PI CASSAT, JAMES E, MBALAVIELE, GABRIEL · 2021 to 2025
$3.4M
Targeting angiogenesis for fracture nonunion treatment under inflammatory diseasesR01AR077616 · NIAMS · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN, SHEN, JIE · 2020 to 2025
$2.7M
Epigenetic Regulation of Bone Regeneration in Inflammatory DiseaseR01AR075860 · NIAMS · WASHINGTON UNIVERSITY · PI SHEN, JIE · 2019 to 2024
$2.6M
Role of gasdermin D in bone resorptionR01AR076758 · NIAMS · WASHINGTON UNIVERSITY · PI MBALAVIELE, GABRIEL · 2020 to 2024
$1.9M
Mechanisms of Physiologic and Pathologic OsteoclastogenesisR01AR072623 · NIAMS · WASHINGTON UNIVERSITY · PI ABU-AMER, YOUSEF · 2018 to 2022
$1.7M
Stem cell therapy for fracture nonunion under inflammatory diseasesR21AR077226 · NIAMS · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID, SHEN, JIE · 2020 to 2021
$376k
NIAID NIH HHS R01 AI161022NIAMS NIH HHS P30 AR074992NIAMS NIH HHS R01 AR049192NIAMS NIH HHS R01 AR050211NIAMS NIH HHS R01 AR072623NIAMS NIH HHS R01 AR075860NIAMS NIH HHS R01 AR076758NIAMS NIH HHS R01 AR077616NIAMS NIH HHS R21 AR077226
6 · The paper itself

Abstract

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of

Indexed as

InflammasomesInterleukin-18AnimalsFracture HealingInterleukin-1betaMicePhosphate-Binding ProteinsPyroptosisInflammasomesInterleukin-18Interleukin-1betaPhosphate-Binding Proteinsbonefracturegasderminimmunologyinflammasomeinflammationmedicinemouseosteoclast

Identifiers

PMID35244027
PMCPMC8923664
OpenAlexW4214863834

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.