BAP1 promotes osteoclast function by metabolic reprogramming.

ABSTRACT: Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1^∆LysM), arrests osteoclast function but not formation. Bap1^∆LysM osteoclasts fail to organize their cytoskeleton which is essential for bone degradation consequently increasing bone mass in both male and female mice. The deubiquitinase activity of BAP1 modifies osteoclast function by metabolic reprogramming. Bap1 deficient osteoclast upregulate the cystine transporter, Slc7a11, by enhan

SUBMITTER: Rohatgi N 

PROVIDER: S-EPMC10516877 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature