Caspase-8 promotes scramblase-mediated phosphatidylserine exposure and fusion of osteoclast precursors.

ABSTRACT: Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts. However, the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood. Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion. Single cell RNA sequencing-based analyses suggested that activation of parts of the apoptotic machinery accompanied the differentiation of osteoclast precursors into mature multinucleated osteoclasts. A subsequent characterization of osteoclast precursors confirmed that RANKL-mediated activation of caspase-8 promoted the non-apoptotic cleavage and activation of downstream effector caspases that translocated to the plasma membra

SUBMITTER: Krishnacoumar B 

PROVIDER: S-EPMC11237014 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature