Caspase-9 is a positive regulator of osteoblastic cell migration identified by diaPASEF proteomics

ABSTRACT: Caspase-9 is traditionally considered as the initiator caspase of the intrinsic apoptotic pathway. In the last 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 non-apoptotic 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/motility and DNA replication/repair. Altered migration was confirmed in MC3T3-E1 cells with 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.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Pavel Bouchal  

LAB HEAD: Pavel Bouchal

PROVIDER: PXD045703 | Pride | 2024-04-17

REPOSITORIES: Pride