Kynurenine Promotes RANKL-Induced Osteoclastogenesis In Vitro by Activating the Aryl Hydrocarbon Receptor Pathway
Nada H Eisa1,2,3, Sakamuri V Reddy4, Ahmed M Elmansi1,2
1Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403, USA.
International Journal of Molecular Sciences
|October 29, 2020
Summary
The tryptophan metabolite kynurenine (KYN) promotes bone loss by increasing osteoclastogenesis, the formation of bone-resorbing cells. Blocking the aryl hydrocarbon receptor (AhR) pathway inhibits this effect, suggesting a therapeutic target for osteoporosis.
Area of Science:
- Biochemistry
- Cell Biology
- Bone Biology
Background:
- Aging is associated with bone loss, partly due to disrupted osteogenesis.
- The tryptophan metabolite kynurenine (KYN) is implicated in aging-related bone loss.
Purpose of the Study:
- To investigate the direct effect of KYN on osteoclastogenesis.
- To elucidate the mechanism underlying KYN-mediated osteoclastogenesis.
- To explore the role of the aryl hydrocarbon receptor (AhR) in KYN-induced osteoclastogenesis.
Main Methods:
- Treatment of Raw 264.7 macrophage cells with KYN and receptor activator of nuclear factor kappa-B ligand (RANKL).
- Analysis of osteoclast differentiation markers, including TRAP staining.
- Assessment of osteoclast transcription factors (c-fos, NFATc1) and bone resorptive activity.
- Inhibition of AhR signaling using an antagonist or siRNA.
Main Results:
- KYN enhances RANKL-induced osteoclast differentiation and multinucleated TRAP+ osteoclast formation.
- KYN upregulates and activates c-fos and NFATc1, increasing bone resorption.
- Blocking AhR signaling inhibits KYN/RANKL-mediated osteoclastogenesis.
Conclusions:
- KYN promotes bone resorption by increasing osteoclastogenesis via the AhR pathway.
- The KYN-AhR pathway is a potential therapeutic target for age-related bone loss and osteoporosis.
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