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Entree


AMPKα1 negatively regulates osteoclastogenesis and mitigates pathological bone loss

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Autor(es):
Ribeiro, Mariana S. P. ; Venturini, Lucas G. R. ; Speck-Hernandez, Cesar A. ; Alabarse, Paulo V. G. ; Xavier, Thais ; Taira, Thaise M. ; Cunha, Fernando Q. ; Fukada, Sandra Y.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: Journal of Biological Chemistry; v. 299, n. 12, p. 8-pg., 2023-12-01.
Resumo

Osteoclasts are specialized cells responsible for bone resorption, a highly energy-demanding process. Focus on osteoclast metabolism could be a key for the treatment of osteolytic diseases including osteoporosis. In this context, AMP-activated protein kinase alpha 1 (AMPK alpha 1), an energy sensor highly expressed in osteoclasts, participates in the metabolic reconfiguration during osteoclast differentiation and activation. This study aimed to elucidate the role of AMPK alpha 1 during osteoclastogenesis in vitro and its impact in bone loss in vivo. Using LysMcre/0AMPKa1f/f animals and LysMcre/0 as control, we evaluated how AMPK alpha 1 interferes with osteoclastogenesis and bone resorption activity in vitro. We found that AMPK alpha 1 is highly expressed in the early stages of osteoclastogenesis. Genetic deletion of AMPK alpha 1 leads to increased gene expression of osteoclast differentiation and fusion markers. In addition, LysMcre/0AMPKa1f/f mice had an increased number and size of differentiated osteoclast. Accordingly, AMPK alpha 1 negatively regulates bone resorption in vitro, as evidenced by the area of bone resorption in LysMcre/0AMPKa1f/f osteoclasts. Our data further demonstrated that AMPK alpha 1 regulates mitochondrial fusion and fission markers upregulating Mfn2 and downregulating DRP1 (dynamics-related protein 1) and that Ctskcre/ 0AMPKa1f/f osteoclasts lead to an increase in the number of mitochondria in AMPKa1-deficient osteoclast. In our in vivo study, femurs from Ctskcre/0AMPKa1f/f animals exhibited bone loss associated with the increased number of osteoclasts, and there was no difference between Sham and ovariectomized group. Our data suggest that AMPK alpha 1 acts as a negative reguovariectomy. (AU)

Processo FAPESP: 19/08568-2 - Investigação do papel de vesículas extracelulares (VEs) na iniciação, propagação, regeneração e modelação da mineralização biológica
Beneficiário:Pietro Ciancaglini
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 17/24073-8 - Papel de OGT em osteoclastos na perda óssea experimental
Beneficiário:Sandra Yasuyo Fukada Alves
Modalidade de apoio: Auxílio à Pesquisa - Regular