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Sclerostin, a 22-kDa glycoprotein that is mainly secreted by the osteocytes, is a soluble inhibitor of canonical Wnt signaling. Therefore, when present at increased concentrations, it leads to an increased bone resorption and decreased bone formation. Serum sclerostin levels are known to be increased in the elderly and in patients with chronic kidney disease. In these patient populations, there is a high incidence of ectopic cardiovascular calcification. These calcifications are strongly associated with cardiovascular morbidity and mortality. Although data are still controversial, it is likely that there is a link between ectopic calcification and serum sclerostin levels. The main question, however, remains whether sclerostin exerts either a protective or deleterious role in the ectopic calcification process.
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http://dx.doi.org/10.3390/ijms21093199 | DOI Listing |
Exp Anim
September 2025
Daiichi Sankyo Co., Ltd.
Chronic kidney disease (CKD) is a complicated systemic disease displaying various pathophysiological symptoms including mineral bone disorder (CKD-MBD). Ideally, early intervention for CKD-MBD would be desirable, however, there is not enough evidence regarding treatment of CKD-MBD, especially in its early stages, due to its multifactorial pathophysiology and the difficulty in generating adequate animal models. In this study, we evaluated the efficacy of a tissue nonspecific alkaline phosphatase (TNAP) inhibitor, SBI-425 in a CKD-MBD animal model, produced by a combination of nephrectomy and high inorganic phosphate (P) diet.
View Article and Find Full Text PDFBiochem Biophys Rep
September 2025
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510100, China.
Pseudoxanthoma elasticum (PXE), caused by pathogenic variants in , is characterized by pathological ectopic calcification with poorly understood mechanisms and no effective therapies. To address this, we developed the first zebrafish model of human PXE by introducing the pathogenic point mutation ( , F2 generation) using the highly efficient zhyA3A-CBE5 cytosine base editor. Three mutant types (Type1-Type3, T1-T3) stratified by calcification severity, exhibited reduced levels of the calcification inhibitors vitamin K1 (VK1) and carboxylated matrix Gla protein (cMGP), which were inversely correlated with the severity of calcification.
View Article and Find Full Text PDFMol Brain
August 2025
Laboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu City, 501-1196, Gifu, Japan.
Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2 mice (9/9 animals) showing no obvious abnormalities, the homozygous Slc20a2 mice exhibited severe calcification at 11 months of age (5/5 animals).
View Article and Find Full Text PDFJ Surg Case Rep
August 2025
Department of Thoracic Surgery at Jersey Shore University Medical Center (JSUMC), 1945 Route 33, Neptune, NJ 07753, United States.
Ectopic pancreas (EP) is a rare congenital anomaly defined as pancreatic tissue lacking anatomical or vascular continuity with the pancreas. Although it occurs in 0.25%-2% of the population, mediastinal EP is exceedingly rare, with fewer than 30 reported cases.
View Article and Find Full Text PDFbioRxiv
July 2025
Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA.
is a rare inherited disorder marked by abnormal calcium phosphate deposition in soft connective tissues, particularly the skin, arteries, and eyes. It is caused by inactivating mutations in the gene, which encodes a hepatic efflux transporter. Loss of ABCC6 function leads to reduced plasma levels of pyrophosphate, a key inhibitor of calcification, thereby promoting ectopic mineralization.
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