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Cited by 1,194Osteoarthritis Treatment and MechanismsProteoglycans and glycosaminoglycans researchProtease and Inhibitor Mechanisms

Osteoarthritis: pathogenic signaling pathways and therapeutic targets

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Yao, Qing, Wu, Xiaohao, Tao, Chu, Gong, Weiyuan, Chen, Mingjue, Qu, Minghao, Zhong, Yiming, He, Tailin +2 more·2023·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-023-01330-wPMC PMC9898571
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Abstract

Osteoarthritis (OA) is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide. OA was believed to be caused by the wearing and tearing of articular cartilage, but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues, which leads to the histological and structural changes of the joint and ends up with the whole tissue dysfunction. Currently, there is no cure for OA, partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the disease. Therefore, a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development. In this review, we first summarize the epidemiology of OA, including its prevalence, incidence and burdens, and OA risk factors. We then focus on the roles and regulation of the pathological signaling pathways, such as Wnt/β-catenin, NF-κB, focal adhesion, HIFs, TGFβ/ΒΜP and FGF signaling pathways, and key regulators AMPK, mTOR, and RUNX2 in the onset and development of OA. In addition, the roles of factors associated with OA, including MMPs, ADAMTS/ADAMs, and PRG4, are discussed in detail. Finally, we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA. Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies.

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  • NF-κB interacts with other signaling pathways implicated in PD, such as the TGF-β and Wnt/β-catenin pathways.

    “Moreover, NF-κB has been shown to interact with other signaling pathways implicated in PD, such as the TGF-β and Wnt/β-catenin pathways.”

    From Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets. (2024) · cites this paper as [68]

    The NF-κB pathway section (page unavailable) reports cross-talk with BMP and Wnt signaling in osteoarthritis chondrocytes; the TGFβ/BMP section identifies BMPs as part of the TGFβ superfamily. The paper does not establish these interactions in PD, nor does the cited passage specifically identify Wnt/β-catenin or TGF-β signaling as the interacting pathways. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Yao, Q., Wu, X., Tao, C., Gong, W., Chen, M., Qu, M., Zhong, Y., He, T., Chen, S., & Xiao, G.
Affiliations
  • Southern University of Science and Technology (CN)
  • Wuhan Union Hospital (CN)
Corresponding author
  • Yao, Qing
  • Xiao, Guozhi
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2023-02-03
Volume
8
Issue
1
Pages
56-56
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-023-01330-w
PMC
PMC9898571
OpenAlex
W4319080389
Cited by
1,194
References
19
Citations by year
2026: 315 · 2025: 445 · 2024: 335 · 2023: 99
FWCI
52.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82261160395, 82230081, 2017B030301018, 81991513, 82250710175)
  • Shenzhen Fundamental Research Program (JCYJ20220818100617036)
  • National Key Research and Development Program of China (2019YFA0906004)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
osteoarthritis, pathogenesis, signaling pathways, therapeutic target, Wnt/β-catenin signaling, NF-κB, focal adhesions, hypoxia-inducible factor, TGF-β/BMP signaling, FGF signaling, AMPK, mTOR, Runx2, matrix metalloproteinases, ADAMTS, ADAMS, proteoglycan 4, articular cartilage, synovial joints, risk factors, biologic therapy, drug development
MeSH terms
Cartilage, Articular, Humans, Osteoarthritis, Signal Transduction, Transforming Growth Factor beta, NF-kappa B

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