Inhibition of caspase-8 cascade restrains the osteoclastogenic fate of bone marrow cells.
Pflugers Arch
; 476(8): 1289-1302, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38833170
ABSTRACT
Osteoclasts are multinucleated cells of hematopoietic origin, with a pivotal role in bone development and remodeling. Failure in osteoclast differentiation and activation leads to various bone disorders; thus, attention has focused on a search of molecules involved in osteoclast regulatory pathways. Caspase-8 appears to be an interesting candidate for further exploration, due to its potential function in bone development and homeostasis. Mouse bone marrow cells were differentiated into osteoclasts by RANKL stimulation. Increased activation of caspase-8 and its downstream executioner caspases (caspase-3 and caspase-6) was found during osteoclastogenesis. Subsequent inhibition of caspase-8, caspase-3, or caspase-6, respectively, during osteoclast differentiation showed distinct changes in the formation of TRAP-positive multinucleated cells and reduced expression of osteoclast markers including Acp5, Ctsk, Dcstamp, and Mmp9. Analysis of bone matrix resorption confirmed significantly reduced osteoclast function after caspase inhibition. The results clearly showed the role of caspases in the proper development of osteoclasts and contributed new knowledge about non-apoptotic function of caspases.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Osteoclastos
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Células de la Médula Ósea
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Diferenciación Celular
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Ligando RANK
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Inhibidores de Caspasas
Límite:
Animals
Idioma:
En
Revista:
Pflugers Arch
Año:
2024
Tipo del documento:
Article
País de afiliación:
República Checa