Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Osteoporosis and osteoblasts cocultured with adipocytes inhibit osteoblast differentiation by downregulating histone acetylation

Texto completo
Autor(es):
Abuna, Rodrigo P. F. [1] ; Almeida, Luciana O. [1] ; Souza, Alann T. P. [1] ; Fernandes, Roger R. [1] ; Sverzut, Thales F. V. [1] ; Rosa, Adalberto L. [1] ; Beloti, Marcio M. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Bone Res Lab, Sch Dent Ribeirao Preto, Ave Cafe S-N, BR-14040904 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Physiology; v. 236, n. 5, p. 3906-3917, MAY 2021.
Citações Web of Science: 2
Resumo

Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of fractures. Thus, we hypothesized that osteoblasts, besides being negatively affected by interacting with adipocytes, reduce the differentiation of neighboring osteoblasts through the same mechanisms that affect osteoblasts under osteoporotic conditions. We investigated the effect of osteoporosis on osteoblast differentiation and the effect of the conditioned medium of osteoblasts cocultured with adipocytes on the differentiation of other osteoblasts. Osteoporosis was induced by orchiectomy in rats and bone marrow mesenchymal stromal cells (MSCs) were differentiated into osteoblasts. Also, the bone marrow and adipose tissue MSCs were obtained from healthy rats and differentiated into osteoblasts and adipocytes, respectively. Messenger RNA expression, in situ alkaline phosphatase activity, and mineralization confirmed the inhibitory effect of osteoporosis on osteoblast differentiation. This harmful effect was mimicked by the in vitro model using the conditioned medium and it was demonstrated that osteoblasts keep the memory of the negative impact of interacting with adipocytes, revealing an unknown mechanism relevant to the osteoporotic bone loss. Finally, we showed the involvement of acetyl-histone 3 (AcH3) in bone homeostasis as its reduction induced by osteoporosis and conditioned medium impaired osteoblast differentiation. The AcH3 involvement was proved by treating osteoblasts with Trichostatin A that recovered the AcH3 expression and osteoblast differentiation capacity in both situations. Together, our findings indicated that AcH3 might be a target for future studies focused on epigenetic-based therapies to treat bone diseases. (AU)

Processo FAPESP: 16/14711-4 - Papel das Vias de Sinalização de Wnt no Potencial Osteogênico de Superfície de Titânio com Nanotopografia
Beneficiário:Rodrigo Paolo Flores Abuna
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 17/12622-7 - Terapia celular: potencial de células-tronco mesenquimais, VEGF-A e BMP-9 para regenerar tecido ósseo
Beneficiário:Adalberto Luiz Rosa
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/14171-0 - Papel das Vias de Sinalização de Wnt no Potencial Osteogênico de Superfície de Titânio com Nanotopografia
Beneficiário:Márcio Mateus Beloti
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/13290-0 - Terapia celular: avaliação do efeito de células-tronco mesenquimais para regenerar tecido ósseo de ratos com Osteoporose, Diabetes Mellitus ou Hipertensão Arterial
Beneficiário:Alann Thaffarell Portilho de Souza
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 18/17356-6 - Efeito da Superfície de Titânio com Nanotopografia sobre a Interação entre Osteoblastos e Osteoclastos
Beneficiário:Márcio Mateus Beloti
Linha de fomento: Auxílio à Pesquisa - Regular