Effects of advanced glycation end-products, diabetes and metformin on the osteoblastic transdifferentiation capacity of vascular smooth muscle cells: In vivo and in vitro studies.

Autor: Molinuevo MS; Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral UNLP-CICPBA, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 50 y 115, 1900 La Plata, Argentina., Cortizo AM; Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral UNLP-CICPBA, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 50 y 115, 1900 La Plata, Argentina. Electronic address: cortizo@biol.unlp.edu.ar., Sedlinsky C; Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral UNLP-CICPBA, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 50 y 115, 1900 La Plata, Argentina. Electronic address: claudia.sedlinsky@gmail.com.
Jazyk: angličtina
Zdroj: Journal of diabetes and its complications [J Diabetes Complications] 2023 Nov; Vol. 37 (11), pp. 108626. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1016/j.jdiacomp.2023.108626
Abstrakt: Aims: Our objective was to study the vascular smooth muscle cells (VSMC) osteoblastic transdifferentiation in AGE exposed cells or those from diabetic animals, and its response to metformin treatment.
Methods: VSMC were obtained from non-diabetic rats, grown with or without AGE; while VSMC of in vivo-ex vivo studies were obtained from non-diabetic control animals (C), diabetic (D), C treated with metformin (M) and D treated with metformin (D-M). We studied the osteoblastic differentiation by evaluating alkaline phosphatase (ALP), type I collagen (Col) and mineral deposit.
Results: In vitro, AGE increased proliferation, migration, and osteoblastic differentiation of VSMC. Metformin cotreatment prevented the AGE induced proliferation and migration. Both AGE and metformin stimulated the expression of ALP and Col. AGE induced mineralization was prevented by metformin. VSMC from D expressed a higher production of Col and ALP. Those from D-M showed an ALP increase vs C and M, and a partial decrease vs D. Cultured in osteogenic medium, ALP, Col and mineralization increased in D vs C, remained unchanged in M, and were prevented in D-M animals.
Conclusion: Both AGE and DM favor VSMC differentiation towards the osteogenic phenotype and this effect can be prevented by metformin.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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