NF-κB Signaling Regulates Physiological and Pathological Chondrogenesis

Abstract

The nuclear factor-κB (NF-κB) is a transcription factor that regulates the expression of genes that control cell proliferation and apoptosis, as well as genes that respond to inflammation and immune responses. There are two means of NF-κB activation: the classical pathway, which involves the degradation of the inhibitor of κBα (IκBα), and the alternative pathway, which involves the NF-κB-inducing kinase (NIK, also known as MAP3K14). The mouse growth plate consists of the resting zone, proliferative zone, prehypertrophic zone, and hypertrophic zone. The p65 (RelA), which plays a central role in the classical pathway, is expressed throughout the cartilage layer, from the resting zone to the hypertrophic zone. Inhibiting the classical NF-κB signaling pathway blocks growth hormone (GH) or insulin-like growth factor (IGF-1) signaling, suppresses cell proliferation, and suppresses bone morphogenetic protein 2 (BMP2) expression, thereby promoting apoptosis. Since the production of autoantibodies and inflammatory cytokines, such as tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, and IL-17, are regulated by the classical pathways and are increased in rheumatoid arthritis (RA), NF-κB inhibitors are used to suppress inflammation and joint destruction in RA models. In osteoarthritis (OA) models, the strength of NF-κB-activation is found to regulate the facilitation or suppression of OA. On the other hand, RelB is involved in the alternative pathway, and is expressed in the periarticular zone during the embryonic period of development. The alternative pathway is involved in the generation of chondrocytes in the proliferative zone during physiological conditions, and in the development of RA and OA during pathological conditions. Thus, NF-κB is an important molecule that controls normal development and the pathological destruction of cartilage.

Anti-Inflammatory Activity of Exopolysaccharides from Phormidium sp. ETS05, the Most Abundant Cyanobacterium of the Therapeutic Euganean Thermal Muds, Using the Zebrafish Model

“…However, deregulation of the NF-κB signaling pathway can play a fundamental role in the pathogenesis of most chronic inflammatory diseases including rheumatoid arthritis [69], cardiovascular disease, inflammatory bowel disease, and neurodegenerative diseases [68].…”

High follicle‐stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/NF‐κB pathway

“…Several AKT substrates have been reported, including NF-jB [23]. NF-jB is a family of transcription factor proteins in which the p65 subunit has been found to be involved in inflammation, apoptosis and matrix degradation processes of chondrocytes [24][25][26][27]. Currently, the NF-jB pathway has been considered as a promising therapeutic target for the treatment of OA.…”

Nuclear Export Protein CSE1L Interacts with P65 and Promotes NSCLC Growth via NF-κB/MAPK Pathway

“…The transcription factor nuclear factor-κB (NF-κB) regulates the expression of a wide variety of genes involved in immune and in ammatory responses, cell proliferation, tumorigenesis, cell survival, and development [36]. The P65 plays a central role in the NF-κB pathway [37]. The protein level of P65 was notably altered in the nucleus when CSE1L was knockdown or overexpressed, and CSE1L was important for stabilization of P65 by protecting it from proteasomal degradation.…”