Inhibition of caspase-8 cascade restrains the osteoclastogenic fate of bone marrow cells.

Autor: Veselá B; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic. veselab.lab@gmail.com.; Department of Physiology, University of Veterinary Sciences Brno, Brno, Czech Republic. veselab.lab@gmail.com., Ševčíková A; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic., Holomková K; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic., Ramešová A; Department of Biological Sciences and Pathobiology, Centre of Biological Sciences, University of Veterinary Medicine Vienna, Vienna, Austria., Kratochvílova A; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic., Sharpe PT; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic.; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK., Matalová E; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic.; Department of Physiology, University of Veterinary Sciences Brno, Brno, Czech Republic.
Jazyk: angličtina
Zdroj: Pflugers Archiv : European journal of physiology [Pflugers Arch] 2024 Aug; Vol. 476 (8), pp. 1289-1302. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1007/s00424-024-02977-2
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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