| Autor: |
Říhová K; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno 602 00, Czech Republic., Lapčík P; Department of Biochemistry, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic., Veselá B; Laboratory of Odontogenesis and Osteogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno 602 00, Czech Republic., Knopfová L; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno 602 00, Czech Republic., Potěšil D; Proteomics Core Facility, Central European Institute for Technology, Masaryk University, Brno 625 00, Czech Republic., Pokludová J; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno 602 00, Czech Republic., Šmarda J; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic., Matalová E; Laboratory of Odontogenesis and Osteogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno 602 00, Czech Republic.; Department of Physiology, Faculty of Veterinary Medicine, University of Veterinary Sciences, Brno 612 42, Czech Republic., Bouchal P; Department of Biochemistry, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic., Beneš P; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno 625 00, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno 602 00, Czech Republic. |
| Abstrakt: |
Caspase-9 is traditionally considered the initiator caspase of the intrinsic apoptotic pathway. In the past decade, however, other functions beyond initiation/execution of cell death have been described including cell type-dependent regulation of proliferation, differentiation/maturation, mitochondrial, and endosomal/lysosomal homeostasis. As previous studies revealed nonapoptotic functions of caspases in osteogenesis and bone homeostasis, this study was performed to identify proteins and pathways deregulated by knockout of caspase-9 in mouse MC3T3-E1 osteoblasts. Data-independent acquisition-parallel accumulation serial fragmentation (diaPASEF) proteomics was used to compare protein profiles of control and caspase-9 knockout cells. A total of 7669 protein groups were quantified, and 283 upregulated/141 downregulated protein groups were associated with the caspase-9 knockout phenotype. The deregulated proteins were mainly enriched for those associated with cell migration and motility and DNA replication/repair. Altered migration was confirmed in MC3T3-E1 cells with the genetic and pharmacological inhibition of caspase-9. ABHD2, an established regulator of cell migration, was identified as a possible substrate of caspase-9. We conclude that caspase-9 acts as a modulator of osteoblastic MC3T3-E1 cell migration and, therefore, may be involved in bone remodeling and fracture repair. |
