ArticleInternational journal of molecular sciences2020
Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Association between the nutritional risk index and postmenopausal osteoporosis in patients with type 2 diabetes mellitus.Frontiers in nutrition · 2026Article
- The role of the kynurenine pathway in cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Article
- The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease.Clinical kidney journal · 2022Article
- What If Not All Metabolites from the Uremic Toxin Generating Pathways Are Toxic? A Hypothesis.Toxins · 2022Review
- Paracrine Kynurenic Pathway Activation in the Bone of Young Uremic Rats Can Antagonize Anabolic Effects of PTH on Bone Turnover and Strength through the Disruption of PTH-Dependent Molecular Signaling.International journal of molecular sciences · 2021Article
- The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging.International journal of molecular sciences · 2020Review
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
An increase in the peripheral synthesis of serotonin and kynurenine, observed during the chronic kidney disease (CKD) course, is negatively associated with bone health. Serotonin and kynurenine are connected by the common precursor, tryptophan. LP533401 is an inhibitor of peripheral serotonin synthesis. This study aimed to establish if the inhibition of serotonin synthesis by LP533401 may affect the kynurenine pathway activity in bone tissue and its potential consequence with regard to osteogenesis and bone mineral status. Nephrectomized rats were treated with LP533401 at a dose of 30 and 100 mg/kg daily for eight weeks. Tryptophan and kynurenine concentrations were determined, and tryptophan 2,3-dioxygenase (TDO) expression was assessed. We discovered the presence of a TDO-dependent, paracrine kynurenic system in the bone of rats with CKD. Its modulation during LP533401 treatment was associated with impaired bone mineral status. Changes in TDO expression affecting the kynurenine pathway activity were related to the imbalance between peripheral serotonin and 25-hydroxyvitamin D. There were also close associations between the expression of genes participating in osteoblastogenesis and activation of the kynurenine pathway in the bones of LP53301-treated rats. Our results represent the next step in studying the role of tryptophan metabolites in renal osteodystrophy.
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