Osteoarthritis: pathogenic signaling pathways and therapeutic targets

Qing Yao1; Xiaohao Wu1; Chu Tao1; Weiyuan Gong1; Mingjue Chen1; Minghao Qu1; Yiming Zhong1; Tailin He1; Sheng Chen2; Guozhi Xiao1

2023-12-01

10.1038/s41392-023-01330-w

Signal Transduction and Targeted Therapy   Impact Factor & Quartile

2095-9907

2059-3635

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.

SCI

English

First ; 共同第一 ; Corresponding

National Key Research and Development Program of China[2019YFA0906004] ; National Natural Science Foundation of China["82230081","82250710175","82172375","81991513","82261160395"] ; Shenzhen Stable Support Plan Program for Higher Education Institutions[20200925150409001] ; Shenzhen Fundamental Research Program[JCYJ20220818100617036] ; Shenzhen Key Laboratory of Cell Microenvironment Grant[ZDSYS20140509142721429] ; Guangdong Provincial Science and Technology Innovation Council[2017B030301018]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000925731100005

SPRINGERNATURE

2-s2.0-85147360694

Scopus

1.Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen 518055, China
2.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

Qing Yao,Xiaohao Wu,Chu Tao,et al. Osteoarthritis: pathogenic signaling pathways and therapeutic targets[J]. Signal Transduction and Targeted Therapy,2023,8(1).

Qing Yao.,Xiaohao Wu.,Chu Tao.,Weiyuan Gong.,Mingjue Chen.,...&Guozhi Xiao.(2023).Osteoarthritis: pathogenic signaling pathways and therapeutic targets.Signal Transduction and Targeted Therapy,8(1).

Qing Yao,et al."Osteoarthritis: pathogenic signaling pathways and therapeutic targets".Signal Transduction and Targeted Therapy 8.1(2023).