Alleviation of Murine Osteoarthritis by Cartilage‐Specific Deletion of IκBζ

Choi, Moon‐Chang; Maruyama, Takashi; Chun, Churl Hong; Park, Yoonkyung

doi:10.1002/art.40514

Cited by 34 publications

(40 citation statements)

References 44 publications

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“…Moreover, IκBζ was shown to form a complex with NF-kB [32]. Thus, IκBζ appears to be a novel player in the pathogenesis of inflammatory stimuli-induced osteoarthritis [31].…”

Section: Role Of Interleukin-1 (Il-1) and Nuclear Factor Kb (Nf-kb) Smentioning

confidence: 99%

“…Nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor zeta (IκBζ) was initially proposed to function as an inhibitory molecule for NF-κB; however, it has been shown that IκBζ also mediates inflammatory signals downstream of IL-1 and TNFα [29,30]. IL-1β upregulated IκBζ expression in chondrocytes, and IκBζ expression was found to be increased in cartilage tissues of patients with osteoarthritis [31]. Cartilage-specific IκBζ-conditional knockout (KO) mice exhibited suppressed development of osteoarthritis.…”

Section: Role Of Interleukin-1 (Il-1) and Nuclear Factor Kb (Nf-kb) Smentioning

confidence: 99%

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Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

Nishimura

Hata

Takahata

et al. 2020

IJMS

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Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 million and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. Interleukin-1 β (IL-1β) leads to osteoarthritis through NF-ĸB, IκBζ, and the Zn2+-ZIP8-MTF1 axis. IL-1, IL-6, and tumor necrosis factor α (TNFα) play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF), parathyroid hormone-related protein (PTHrP), and Indian hedgehog, play roles in regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling pathways cause genetic disorders in cartilage and skeletal tissues. Fibrodysplasia ossificans progressive, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. Mechanistic target of rapamycin kinase (mTOR) inhibitors can prevent ectopic ossification induced by ACVR1 mutations. C-type natriuretic peptide is currently the most promising therapy for achondroplasia and related autosomal genetic diseases that manifest severe dwarfism. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels has enlightened the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

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“…Moreover, IκBζ was shown to form a complex with NF-kB [32]. Thus, IκBζ appears to be a novel player in the pathogenesis of inflammatory stimuli-induced osteoarthritis [31].…”

Section: Role Of Interleukin-1 (Il-1) and Nuclear Factor Kb (Nf-kb) Smentioning

confidence: 99%

Section: Role Of Interleukin-1 (Il-1) and Nuclear Factor Kb (Nf-kb) Smentioning

confidence: 99%

Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

Nishimura

Hata

Takahata

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…Moreover, IκBζ was shown to form a complex with NF-ĸB [26]. Thus, IκBζ appears to be a novel player in the pathogenesis of inflammatory stimuli-induced osteoarthritis [25].…”

Section: Role Of Nf-ĸb Signaling In Osteoarthritismentioning

confidence: 99%

“…Nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor zeta (IκBζ) was initially proposed to function as an inhibitory molecule for NF-κB; however, it has been shown that IκBζ also mediates inflammatory signals as downstream of IL-1 and TNFα [23,24]. IL-1β upregulated IκBζ expression in chondrocytes, and IκBζ expression was found to be increased in cartilage tissues of patients with osteoarthritis [25]. Cartilage-specific IκBζ conditional-knockout (KO) mice exhibited suppressed development of osteoarthritis.…”

Section: Role Of Nf-ĸb Signaling In Osteoarthritismentioning

confidence: 99%

“…IκBζ, which plays an important role in the differentiation of IL-17-producing helper T cells, is purportedly involved in rheumatoid arthritis through interactions with ROR nuclear receptors [80]. Although the precise relationship between NF-κB and IκBζ, both of which are activated by IL-1 [25], remains elusive, the latter may also be a potential therapeutic target for rheumatoid arthritis.…”

Section: Transcription Factors Involved In Rheumatoid Arthritismentioning

confidence: 99%

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Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

Nishimura¹,

Hata²,

Takahata³

et al. 2020

Preprint

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Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. IL-1β also leads to osteoarthritis through NF-ĸB, IκBζ, and Zn2+-ZIP8-MTF1 axis. IL-1, IL-6, and TNFα play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as BMP, FGF, PTHrP, and Indian hedgehog, play roles regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling cause genetic disorders in cartilage and skeletal tissues. FOP, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. mTOR inhibitors were found to prevent ectopic ossification by ACVR1 mutations. ACH and related diseases are autosomal genetic diseases, which manifest severe dwarfism. CNP is currently the most promising therapy for ACH. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels sheds light on the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

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

et al. 2020

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Knee osteoarthritis (KOA) is prevalent in postmenopausal women and a cause of pain and disability in elderly populations. Here, we report high follicle‐stimulating hormone (FSH) levels across postmenopausal female KOA patients aged 50–60 years. We speculate FSH might damage cartilage tissues through the phosphoinositide 3‐kinase/AKT/nuclear factor kappa B pathway. Our findings suggest that FSH modulation holds promise as a novel treatment for postmenopausal female KOA patients aged 50–60 years.

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Alleviation of Murine Osteoarthritis by Cartilage‐Specific Deletion of IκBζ

Abstract: These findings demonstrate a critical role for IκBζ in OA pathogenesis. Inhibition of IκBζ function might be an effective therapeutic approach for OA treatment.

Cited by 34 publications

References 44 publications

Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

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

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