Normoglycemia partially recovers the disrupted osteoblast differentiation of mesenchymal stem cells induced by type 1 but not type 2 diabetes mellitus

Type 1 (T1DM) and type 2 (T2DM) diabetes mellitus are characterized by changes in glucose metabolism and cause bone damage via a variety of mechanisms, including effects on osteoblasts. We aimed to evaluate the osteoblast differentiation of mesenchymal stem cells (MSCs) from rats with T1DM or T2DM a...

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Detalhes bibliográficos
Autores: Weffort, Denise, Adolpho, Leticia F., Souza, Alann T. P., Freitas, Gileade P., Lopes, Helena B., Oliveira, Fabiola S., Bighetti-Trevisan, Rayana L., Pitol-Palin, Leticia [UNESP], Matsushita, Doris H. [UNESP], Okamoto, Roberta [UNESP], Beloti, Marcio M., Rosa, Adalberto L.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Brasil
Recursos:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/301275
Acesso em linha:http://dx.doi.org/10.1002/jcb.30434
https://hdl.handle.net/11449/301275
Access Level:acceso abierto
Palavra-chave:bone
diabetes mellitus
hyperglycemia
mesenchymal stem cells
osteoblasts
Descrição
Resumo:Type 1 (T1DM) and type 2 (T2DM) diabetes mellitus are characterized by changes in glucose metabolism and cause bone damage via a variety of mechanisms, including effects on osteoblasts. We aimed to evaluate the osteoblast differentiation of mesenchymal stem cells (MSCs) from rats with T1DM or T2DM and the effects of removing the hyperglycemic stimulus on the osteogenic potential of these cells. MSCs from healthy rats were cultured in normoglycemic medium, whereas MSCs from rats with T1DM or T2DM were cultured in hyperglycemic or normoglycemic medium. T1DM and T2DM reduced osteoblast differentiation of MSCs grown in hyperglycemic media, with T1DM having a more pronounced effect, as evidenced by alkaline phosphatase activity, RUNX2 protein expression, and extracellular matrix mineralization, and modulated the gene expression of several components of the bone morphogenetic protein signaling pathway. The restoration of the normoglycemic environment partially recovers the osteogenic potential of MSCs from rats with T1DM but not with T2DM. Our findings highlight the need for specific therapies to treat T1DM- or T2DM-induced bone loss, as both disrupt osteoblast differentiation at distinct levels and likely through different mechanisms.

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