Orchiectomy sensitizes cortical bone in male mice to the harmful effects of kynurenine

Bensreti, Husam; Yu, Kanglun; Alhamad, Dima W.; Shaver, Joseph R.; Kaiser, Helen; Zhong, Roger; Whichard, William C.; Parker, E.J.; Grater, Lindsey; Faith, Hayden; Johnson, Maribeth H.; Cooley, Marion A.; Fulzele, Sadanand; Hill, W. David; Isales, Carlos M.; Hamrick, Mark W.; McGee‐Lawrence, Meghan E.

doi:10.1016/j.bone.2023.116811

Cited by 5 publications

(2 citation statements)

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“…( 24 ) similarly demonstrated that the tryptophan byproduct kynurenine, accumulating with age, can induce bone loss. Testosterone may play an important role in regulating Kyn/AhR signaling in musculoskeletal tissues, suggesting that crosstalk between androgenic steroids and Kyn signaling may influence age-related musculoskeletal frailty ( 25 ). Pyroglutamic acid, a cyclic nonprotein-derived amino acid formed through glutamine or glutamate deamidation or dehydration, respectively ( 26 ), modulates bone metabolism via osteoclasts and is convertible to glutamate ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Discovery of potential biomarkers for osteoporosis using LC/GC−MS metabolomic methods

Wu,

Yuan,

Han

et al. 2024

Front. Endocrinol.

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PurposeFor early diagnosis of osteoporosis (OP), plasma metabolomics of OP was studied by untargeted LC/GC−MS in a Chinese elderly population to find possible diagnostic biomarkers.MethodsA total of 379 Chinese community-dwelling older adults aged ≥65 years were recruited for this study. The BMD of the calcaneus was measured using quantitative ultrasound (QUS), and a T value ≤-2.5 was defined as OP. Twenty-nine men and 47 women with OP were screened, and 29 men and 36 women were matched according to age and BMI as normal controls using propensity matching. Plasma from these participants was first analyzed by untargeted LC/GC−MS, followed by FC and P values to screen for differential metabolites and heatmaps and box plots to differentiate metabolites between groups. Finally, metabolic pathway enrichment analysis of differential metabolites was performed based on KEGG, and pathways with P ≤ 0.05 were selected as enrichment pathways.ResultsWe screened metabolites with FC>1.2 or FC<1/1.2 and P<0.05 and found 33 differential metabolites in elderly men and 30 differential metabolites in elderly women that could be potential biomarkers for OP. 2-Aminomuconic acid semialdehyde (AUC=0.72, 95% CI 0.582-0.857, P=0.004) is highly likely to be a biomarker for screening OP in older men. Tetradecanedioic acid (AUC=0.70, 95% CI 0.575-0.818, P=0.004) is highly likely to be a biomarker for screening OP in older women.ConclusionThese findings can be applied to clinical work through further validation studies. This study also shows that metabolomic analysis has great potential for application in the early diagnosis and recurrence monitoring of OP in elderly individuals.

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Section: Discussionmentioning

confidence: 99%

Discovery of potential biomarkers for osteoporosis using LC/GC−MS metabolomic methods

Wu,

Yuan,

Han

et al. 2024

Front. Endocrinol.

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“…Kyn has been implicated in several age-related disorders including neurodegeneration, osteoporosis, sarcopenia, and inflammation (16)(17)(18)(19)(20). Treatment of rodents with exogenous Kyn, either through diet or intraperitoneal injections, can induce bone loss (17,21,22) and muscle atrophy (19). An increase in IDO activity has been linked to an increased mortality rate in humans (23), and frailty is associated with a marked increase in the Kyn/Trp ratio (24)(25)(26)(27).…”

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confidence: 99%

The kynurenine pathway in HIV, frailty and inflammaging

Sultana,

Elengickal,

Bensreti

et al. 2023

Front. Immunol.

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Kynurenine (Kyn) is a circulating tryptophan (Trp) catabolite generated by enzymes including IDO1 that are induced by inflammatory cytokines such as interferon-gamma. Kyn levels in circulation increase with age and Kyn is implicated in several age-related disorders including neurodegeneration, osteoporosis, and sarcopenia. Importantly, Kyn increases with progressive disease in HIV patients, and antiretroviral therapy does not normalize IDO1 activity in these subjects. Kyn is now recognized as an endogenous agonist of the aryl hydrocarbon receptor, and AhR activation itself has been found to induce muscle atrophy, increase the activity of bone-resorbing osteoclasts, decrease matrix formation by osteoblasts, and lead to senescence of bone marrow stem cells. Several IDO1 and AhR inhibitors are now in clinical trials as potential cancer therapies. We propose that some of these drugs may be repurposed to improve musculoskeletal health in older adults living with HIV.

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