Calcium isotope fractionation by osteoblasts and osteoclasts, across endothelial and epithelial cell barriers, and with binding to proteins

• Verfasst von: Töpfer, Eva Teresa [VerfasserIn]
• Verfasst von: Rott, Jeremy [VerfasserIn]
• Verfasst von: Bartosova, Maria [VerfasserIn]
• Verfasst von: Kolevica, Ana [VerfasserIn]
• Verfasst von: Machuca-Gayet, Irma [VerfasserIn]
• Verfasst von: Heuser, Alexander [VerfasserIn]
• Verfasst von: Rabe, Michael [VerfasserIn]
• Verfasst von: Shroff, Rukshana [VerfasserIn]
• Verfasst von: Bacchetta, Justine [VerfasserIn]
• Verfasst von: Zarogiannis, Sotirios G. [VerfasserIn]
• Verfasst von: Eisenhauer, Anton [VerfasserIn]
• Verfasst von: Schmitt, Claus P. [VerfasserIn]
• Titel: Calcium isotope fractionation by osteoblasts and osteoclasts, across endothelial and epithelial cell barriers, and with binding to proteins
• Verf.angabe: Eva Teresa Toepfer, Jeremy Rott, Maria Bartosova, Ana Kolevica, Irma Machuca-Gayet, Alexander Heuser, Michael Rabe, Rukshana Shroff, Justine Bacchetta, Sotirios G. Zarogiannis, Anton Eisenhauer, and Claus Peter Schmitt
• E-Jahr: 2021
• Jahr: May 12, 2021
• Umfang: 12 S.
• Fussnoten: Gesehen am 02.12.2021
• Titel Quelle: Enthalten in: American journal of physiology. Regulatory, integrative and comparative physiology
• Ort Quelle: Bethesda, Md. : American Physiological Society, 1977
• Jahr Quelle: 2021
• Band/Heft Quelle: 321(2021), 1, Seite R29-R40
• ISSN Quelle: 1522-1490
• DOI: doi:10.1152/ajpregu.00334.2020
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1780082681

Abstract

Timely and accurate diagnosis of osteoporosis is essential for adequate therapy. Calcium isotope ratio (δ Ca-44/42) determination has been suggested as a sensitive, noninvasive, and radiation-free biomarker for the diagnosis of osteoporosis, reflecting bone calcium balance. The quantitative diagnostic is based on the calculation of the δ Ca-44/42 difference between blood, urine, and bone. The underlying cellular processes, however, have not been studied systematically. We quantified calcium transport and δ Ca-44/42 fractionation during in vitro bone formation and resorption by osteoblasts and osteoclasts and across renal proximal tubular epithelial cells (HK-2), human vein umbilical endothelial cells (HUVECs), and enterocytes (Caco-2) in transwell systems and determined transepithelial electrical resistance characteristics. δ Ca-44/42 fractionation was furthermore quantified with calcium binding to albumin and collagen. Calcified matrix formed by osteoblasts was isotopically lighter than culture medium by −0.27 ± 0.03‰ within 5 days, while a consistent effect of activated osteoclasts on δ Ca-44/42 could not be demonstrated. A transient increase in δ Ca-44/42 in the apical compartment by 0.26‰ occured across HK-2 cells, while δ Ca-44/42 fractionation was small across the HUVEC barrier and absent with Caco-2 enterocytes, and with binding of calcium to albumin and collagen. In conclusion, δ Ca-44/42 fractionation follows similar universal principles as during inorganic mineral precipitation; osteoblast activity results in δ Ca-44/42 fractionation. δ Ca-44/42 fractionation also occurs across the proximal tubular cell barrier and needs to be considered for in vivo bone mineralization modeling. In contrast, the effect of calcium transport across endothelial and enterocyte barriers on blood δ Ca-44/42 should be low and is absent with physiochemical binding of calcium to proteins.