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  • Caspase-9 Is a Positive Regulator of Osteoblastic Cell Migration Identified by diaPASEF Proteomics.

Caspase-9 Is a Positive Regulator of Osteoblastic Cell Migration Identified by diaPASEF Proteomics.

Journal of proteome research (2024-03-19)
Kamila Říhová, Petr Lapčík, Barbora Veselá, Lucia Knopfová, David Potěšil, Jana Pokludová, Jan Šmarda, Eva Matalová, Pavel Bouchal, Petr Beneš
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Caspase-3/7 Inhibitor II, The Caspase-3/7 Inhibitor II, also referenced under CAS 775289-20-8, controls the biological activity of Caspase-3/7. This small molecule/inhibitor is primarily used for Cancer applications.
Sigma-Aldrich
Caspase-9 Inhibitor II, Cell-Permeable, The Caspase-9 Inhibitor II, Cell-Permeable controls the biological activity of Caspase-9. This small molecule/inhibitor is primarily used for Cancer applications.