Crosstalk between Cytokine RANKL and AhR Signalling in Osteoclasts Controls Bone Homeostasis

Izawa, Takashi; Arakaki, Rieko; Ishimaru, Naozumi

doi:10.4172/2576-3881.1000114

Cited by 3 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aryl hydrocarbon receptor (AhR) has been shown to play an important role in osteoclast differentiation through its involvement in the RANK/c-Fos axis. Its expression increases during osteoclast differentiation, and the BMMs from the AhR knockout mice exhibit an impaired RANKL-induced activation of MAPKs and NF-κB, as well as c-Fos induction [ 39 , 40 ]. We observed that EEEA inhibits the RANKL-induced protein expression of c-Fos but does not affect its mRNA expression ( Figure 3 A,B).…”

Section: Resultsmentioning

confidence: 99%

Euonymus alatus (Thunb.) Siebold Prevents Osteoclast Differentiation and Osteoporosis

Lee,

Jang,

Kim

et al. 2023

Nutrients

View full text Add to dashboard Cite

Euonymus alatus (Thunb.) Siebold, a traditional medicinal plant, has been used in China and several other Asian countries to address a variety of health concerns. The extensive research conducted on E. alatus is driven by its diverse pharmacological applications. However, its biological effects on osteoclastogenesis and osteoporosis have not been previously studied. In this research, we investigated the impact of an ethanolic extract of E. alatus (EEEA) on osteoclast differentiation and function as well as estrogen deficiency-induced bone loss. We found that EEEA inhibits osteoclast differentiation by downregulating the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoclast-supporting cells and by directly impeding RANKL-mediated signaling pathways for osteoclastogenesis in precursor cells. In addition, EEEA inhibited the bone-resorptive function of mature osteoclasts in vitro. Furthermore, oral administration of EEEA significantly alleviated bone loss in an ovariectomy-induced osteoporosis mouse model. Additionally, we identified phytochemicals in EEEA that have suppressive effects on osteoclast differentiation and bone loss. Collectively, these results suggest that EEEA holds potential as a biotherapeutic candidate for anti-postmenopausal osteoporosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Euonymus alatus (Thunb.) Siebold Prevents Osteoclast Differentiation and Osteoporosis

Lee,

Jang,

Kim

et al. 2023

Nutrients

View full text Add to dashboard Cite

show abstract

New insights into benzo[⍺]pyrene osteotoxicity in zebrafish

Tarasco

Gavaia

Bensimon-Brito

et al. 2021

Ecotoxicology and Environmental Safety

View full text Add to dashboard Cite

Kynurenine Promotes RANKL-Induced Osteoclastogenesis In Vitro by Activating the Aryl Hydrocarbon Receptor Pathway

Eisa

Reddy

Elmansi

et al. 2020

IJMS

View full text Add to dashboard Cite

There is increasing evidence of the involvement of the tryptophan metabolite kynurenine (KYN) in disrupting osteogenesis and contributing to aging-related bone loss. Here, we show that KYN has an effect on bone resorption by increasing osteoclastogenesis. We have previously reported that in vivo treatment with KYN significantly increased osteoclast number lining bone surfaces. Here, we report the direct effect of KYN on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in Raw 264.7 macrophage cells, and we propose a potential mechanism for these KYN-mediated effects. We show that KYN/RANKL treatment results in enhancement of RANKL-induced osteoclast differentiation. KYN drives upregulation and activation of the key osteoclast transcription factors, c-fos and NFATc1 resulting in an increase in the number of multinucleated TRAP+ osteoclasts, and in hydroxyapatite bone resorptive activity. Mechanistically, the KYN receptor, aryl hydrocarbon receptor (AhR), plays an important role in the induction of osteoclastogenesis. We show that blocking AhR signaling using an AhR antagonist, or AhR siRNA, downregulates the KYN/RANKL-mediated increase in c-fos and NFATc1 and inhibits the formation of multinucleated TRAP + osteoclasts. Altogether, this work highlights that the novelty of the KYN and AhR pathways might have a potential role in helping to regulate osteoclast function with age and supports pursuing additional research to determine if they are potential therapeutic targets for the prevention or treatment of osteoporosis.

show abstract

Crosstalk between Cytokine RANKL and AhR Signalling in Osteoclasts Controls Bone Homeostasis

Cited by 3 publications

References 51 publications

Euonymus alatus (Thunb.) Siebold Prevents Osteoclast Differentiation and Osteoporosis

Euonymus alatus (Thunb.) Siebold Prevents Osteoclast Differentiation and Osteoporosis

New insights into benzo[⍺]pyrene osteotoxicity in zebrafish

Kynurenine Promotes RANKL-Induced Osteoclastogenesis In Vitro by Activating the Aryl Hydrocarbon Receptor Pathway

Contact Info

Product

Resources

About