Abstract
Osteoarthritis (OA) is a type of joint disease associated with wear and tear, inflammation, and aging. Mechanical stress along with synovial inflammation promotes the degradation of the extracellular matrix in the cartilage, leading to the breakdown of joint cartilage. The nuclear factor-kappaB (NF-κB) transcription factor has long been recognized as a disease-contributing factor and, thus, has become a therapeutic target for OA. Because NF-κB is a versatile and multi-functional transcription factor involved in various biological processes, a comprehensive understanding of the functions or regulation of NF-κB in the OA pathology will aid in the development of targeted therapeutic strategies to protect the cartilage from OA damage and reduce the risk of potential side-effects. In this review, we discuss the roles of NF-κB in OA chondrocytes and related signaling pathways, including recent findings, to better understand pathological cartilage remodeling and provide potential therapeutic targets that can interfere with NF-κB signaling for OA treatment.
Highlights
Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability that reduces the quality of life and causes economic loss [1]
The stimulatory factors that bind to NF-κB subunits include IκBζ, transcription factor 4 (TCF4), SRC-associated in mitosis of 68 kDa (SAM68), and karyopherin alpha 2 (KPNA2)
In chondrocytes, elevated IκBζ forms a complex with the NF-κB p65, p50, and p52 subunits in response to IL-1β and strongly augments NF-κB-dependent transcriptional responses including catabolic genes [16]
Summary
Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability that reduces the quality of life and causes economic loss [1] It occurs when cartilage breaks down and allows bones to rub against each other. No licensed disease-modifying drugs are currently available [6], many clinical trials using the intra-articular (IA) delivery method have been conducted, including treatments with hyaluronic acid, glucocorticoids, biologic agents targeting pro-inflammatory cytokines, and cell therapies using tissue explants, cell concentrates, or mesenchymal stem cells [7,8]. Defining the risk factors that cause OA initiation and progression may reveal biomarkers and therapeutic targets for this disease. This review discusses recent findings related to OA-associated NF-κB signaling, including those regarding the IκBζ protein
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