Unlabelled: Patients with endogenous hypercortisolism have higher sclerostin, but do not differ in Dickkopf 1 (Dkk1) or secreted frizzled-related protein 1 (SFRP1) levels as compared to healthy control.
Introduction: Endogenous Cushing's syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of the Wnt/β-catenin signaling pathway (sclerostin, Dkk1, SFRP1) in patients with CS versus healthy individuals.
Methods: Forty patients with clinically and biochemically evident CS and 40 sex-, age-, and body mass index-matched healthy subjects provided fasting serum samples for sclerostin, SFRP1 and Dkk1, along with bone turnover markers.
Results: Patients with CS had higher sclerostin levels (34.5 (30.3-37.1) pmol/L) versus healthy individuals (29.9 (24.3-36.8) pmol/L) (p = 0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper limits of the healthy control. The odds of sclerostin levels being higher than 30 pmol/L were greater in patients with CS as compared with the odds in healthy subjects (odds ratio = 3.81 95 % confidence interval 1.45-10.02) (p = 0.01). It coexisted with suppressed bone formation and unchanged bone resorption markers. Dkk1, SFRP1 did not differ from the control group.
Conclusions: Of all the tested proteins (sclerostin, Dkk1, SFRP1), only sclerostin showed a significant difference when contrasting CS with healthy subjects. Hypercortisolism might prevent the down-regulation of sclerostin. Targeting sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with CS.
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http://dx.doi.org/10.1007/s00198-013-2268-y | DOI Listing |
Bioorg Chem
January 2025
Department of Zoology, Aligarh Muslim University, Aligarh 202002, India. Electronic address:
Small molecules are emerging as potential candidates for treating osteoporosis by activating canonical Wnt signaling. These candidates work either by inhibiting DKK-1, sclerostin, SFRP-1, NOTUM, and S1P lyase or by preventing β-catenin degradation through inhibition of GSK-3β, or by targeting Dvl-CXXC5 and axin/β-catenin interactions. While many of these anti-osteoporotic small molecules are in preclinical development, the paucity of FDA-approved small molecules, or promising candidates, that have progressed to clinical trials for treating bone disorders through this mechanism poses a challenge.
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August 2023
Department of Stomatology, Shenzhen Longhua District Central Hospital, Shenzhen, China.
Epithelial-mesenchymal transition (EMT) is linked to an unfavorable prognosis in oral squamous cell carcinoma (OSCC). Here, we aimed to develop an EMT gene signature for OSCC prognosis. In TCGA dataset, prognosis-related EMT genes with < 0.
View Article and Find Full Text PDFInt J Mol Sci
August 2023
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVAL, 39012 Santander, Spain.
The evidence sustaining the regenerative properties of mesenchymal stem cells' (MSCs) secretome has prompted a paradigm change, where MSCs have shifted from being considered direct contributors to tissue regeneration toward being seen as cell factories for producing biotech medicines. We have previously designed a method to prime MSCs towards osteogenic differentiation by silencing the Wnt/β-Catenin inhibitor . This approach produces a significant increase in bone formation in osteoporotic mice.
View Article and Find Full Text PDFJ Pers Med
June 2023
Research Department, Rinaldi Fontani Foundation, 50144 Florence, Italy.
Human breast adenocarcinoma is a form of cancer which has the tendency to metastasize to other tissues, including bones, lungs, brain, and liver. Several chemotherapeutic drugs are used to treat breast tumors. Their combination is used to simultaneously target different mechanisms involved in cell replication.
View Article and Find Full Text PDFNeuroscience
August 2023
Laboratory of Cognition and Memory Neurobiology, Brain Institute, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - Bldg. 63, 3rd floor, 90610-000 Porto Alegre, RS, Brazil; Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681 - Bldg. 40, 8th floor, 90610-000 Porto Alegre, RS, Brazil. Electronic address:
Memories already consolidated when reactivated return to a labile state and can be modified, this process is known as reconsolidation. It is known the Wnt signaling pathways can modulate hippocampal synaptic plasticity as well as learning and memory. Yet, Wnt signaling pathways interact with NMDA (N-methyl-D-aspartate) receptors.
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