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Cited by 69Osteoarthritis Treatment and MechanismsBone Metabolism and DiseasesProteoglycans and glycosaminoglycans research

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Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints

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Zhao, Lan, Lai, Yumei, Jiao, Hongli, Huang, Jian·2024·Nature Communications
DOI 10.1038/s41467-024-47633-6PMC PMC11018862

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Abstract

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.

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Metadata

Authors
Zhao, L., Lai, Y., Jiao, H., & Huang, J.
Affiliations
Rush University Medical Center (US)
Corresponding author
Huang, Jian
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-04-15
Volume
15
Issue
1
Pages
3225-3225
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-47633-6
PMC
PMC11018862
OpenAlex
W4394818993
Cited by
69
References
5
Citations by year
2026: 28 · 2025: 30 · 2024: 11
FWCI
22.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070222, R01AR070222-04S1)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Keywords
nerve growth factor receptor, osteoarthritis, joint remodeling, joint repair, NF-κB activation, TNF-α, RANKL, subchondral bone, osteophytes, bone formation, bone resorption, cartilage, inflammation, skeletal progenitor cells

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