The potential roles of JAK/STAT signaling in the progression of osteoarthritis

Zhou, Qingluo; Ren, Qun; Jiao, Linhui; Huang, Jishang; Yi, Jun; Chen, Jincai; Lai, Jinliang; Ji, Guanglin; Zheng, Tiansheng

doi:10.3389/fendo.2022.1069057

Cited by 23 publications

(20 citation statements)

References 149 publications

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“…Phosphorylated STAT proteins then bind to form STAT-STAT dimers, which can bind to DNA and regulate gene expression [ 165 ]. The STAT-STAT dimers can then be deactivated through the dephosphorylation [ 169 ]. In the noncanonical JAK/STAT signaling pathway, most STAT proteins localize to the mitochondria, and STAT3 localizes to the ER to attenuate the apoptosis [ 170 ].…”

Section: Modulation Of Cell Death In Osteoarthritismentioning

confidence: 99%

“…IL-6 is also important for regulating the JAK/STAT pathway in OA; it can make M1 phenotype macrophages more active, and these macrophages can create an excessive inflammatory response, causing more severe symptoms. In contrast, IL-4 and IL-13 can activate M2 phenotype macrophages through the JAK/STAT3 pathway; these macrophages have anti-inflammatory effects that can reduce the symptoms of OA [ 169 ].…”

Section: Modulation Of Cell Death In Osteoarthritismentioning

confidence: 99%

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The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

Liu

Pan

et al. 2023

IJMS

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Osteoarthritis (OA) is a worldwide chronic disease that can cause severe inflammation to damage the surrounding tissue and cartilage. There are many different factors that can lead to osteoarthritis, but abnormally progressed programmed cell death is one of the most important risk factors that can induce osteoarthritis. Prior studies have demonstrated that programmed cell death, including apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and cuproptosis, has a great connection with osteoarthritis. In this paper, we review the role of different types of programmed cell death in the generation and development of OA and how the different signal pathways modulate the different cell death to regulate the development of OA. Additionally, this review provides new insights into the radical treatment of osteoarthritis rather than conservative treatment, such as anti-inflammation drugs or surgical operation.

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Section: Modulation Of Cell Death In Osteoarthritismentioning

confidence: 99%

Section: Modulation Of Cell Death In Osteoarthritismentioning

confidence: 99%

The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

Liu

Pan

et al. 2023

IJMS

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“…There are three common death receptor signaling pathways that all involved in chondrocyte apoptosis: Fas, TNFR1, and TRAIL, and corresponding death receptor‐ligands: Fas–Fas L, TNFR1‐TNF, and TRAIL1‐TRAIL 32–34 . In addition, JAK/STAT signaling pathway mediated chondrocyte apoptosis was revealed in both OA and rheumatoid arthritis 35,36 . PI3K/AKT/mTOR, as a classical signaling axis regulating autophagy, has also been shown to participate in chondrocyte renewal and inhibit apoptosis 37 .…”

Section: Apoptosismentioning

confidence: 99%

“…[32][33][34] In addition, JAK/STAT signaling pathway mediated chondrocyte apoptosis was revealed in both OA and rheumatoid arthritis. 35,36 PI3K/AKT/mTOR, as a classical signaling axis regulating autophagy, has also been shown to participate in chondrocyte renewal and inhibit apoptosis. 37 Moreover, endoplasmic reticulum (ER) stress also causes chondrocyte apoptosis by interfering with chondrocyte homeostasis and initiating unfolded protein response.…”

Section: The Signal Pathways Of Apoptosismentioning

confidence: 99%

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

Xiang

Zheng

Liu

et al. 2023

Orthopaedic Surgery

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Osteoarthritis (OA) causes pain and disability in the elderly and has placed a severe burden on healthcare worldwide. Excessive death and decreased density of chondrocytes are recognized as the major pathological characteristic of OA. Chondrocytes have been shown to have multiple forms of death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. The excessive death of chondrocytes often forms a vicious circle with imbalanced chondrocytes extracellular matrix (ECM) metabolism. Therefore, inhibiting chondrocytes excessive death has become a key point that cannot be ignored in the development of OA treatment strategies. We summarized recent studies on the functions and mechanisms of different modes of chondrocyte death and potential therapeutic strategies for OA and offered our views. This may provide direction and theoretical support for formulating OA treatment strategies in the future.

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“…Therefore, inflammasomes are an attractive therapeutic target against PTOA. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) is an intracellular signaling pathway downstream of multiple inflammatory cytokines in OA [49] . STAT3 in particular responds to IL-6 and binds the IL-6 promoter in the nucleus, thus creating a positive feedback loop of inflammatory signaling via the IL-6/JAK/STAT3 pathway [50] .…”

Section: Pathogenesis-synovial and Chondrocyte Inflammatory Responsementioning

confidence: 99%

Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2

Riggs,

Sankar

2023

Immunometabolism

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Post-traumatic osteoarthritis (PTOA) is a multifactorial disease of the cartilage, synovium, and subchondral bone resulting from direct joint trauma and altered joint mechanics after traumatic injury. There are no current disease-modifying therapies for PTOA, and early surgical interventions focused on stabilizing the joint do not halt disease progression. Chronic pain and functional disability negatively affect the quality of life and take an economic toll on affected patients. While multiple mechanisms are at play in disease progression, joint inflammation is a key contributor. Impact-induced mitochondrial dysfunction and cell death or altered joint mechanics after trauma culminate in inflammatory cytokine release from synoviocytes and chondrocytes, cartilage catabolism, suppression of cartilage anabolism, synovitis, and subchondral bone disease, highlighting the complexity of the disease. Current understanding of the cellular and molecular mechanisms underlying the disease pathology has allowed for the investigation of a variety of therapeutic strategies that target unique apoptotic and/or inflammatory processes in the joint. This review provides a concise overview of the inflammatory and apoptotic mechanisms underlying PTOA pathogenesis and identifies potential therapeutic targets to mitigate disease progression. We highlight Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a serine/threonine protein kinase that was recently identified to play a role in murine and human osteoarthritis pathogenesis by coordinating chondrocyte inflammatory responses and apoptosis. Given its additional effects in regulating macrophage inflammatory signaling and bone remodeling, CaMKK2 emerges as a promising disease-modifying therapeutic target against PTOA.

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The potential roles of JAK/STAT signaling in the progression of osteoarthritis

Cited by 23 publications

References 149 publications

The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2

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