| Texto completo | |
| 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 |