Summary of Study ST002850

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001784. The data can be accessed directly via it's Project DOI: 10.21228/M83T50 This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002850
Study TitleBap1 Promotes Osteoclast Function by Metabolic Reprogramming
Study TypeUntargeted Metabolomics
Study SummaryTreatment of osteoporosis most 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, bone mass increases in the mutant mice. We find the deubiquitinase activity of Bap1 regulates osteoclast function by metabolic reprogramming. Bap1 deficient osteoclast lineage cells upregulate the cystine transporter, Slc7a11, by enhanced H2Aub occupancy of its promoter. SLC7A11 regulates cellular ROS levels and redirects the mitochondrial metabolites away from the TCA cycle, both of which are necessary for osteoclast function. Thus in osteoclasts, Bap1 appears to regulate epigenetic-metabolic axis and is a potential target to reduce bone degradation while maintaining osteogenesis in osteoporotic patients.
Washington University in St. Louis
DepartmentPathology and Immunology, Medicine, Chemistry
LaboratoryTeitelbaum and Patti Laboratories
Last NameCho
First NameKevin
Address1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA
Submit Date2023-08-26
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-09-11
Release Version1
Kevin Cho Kevin Cho application/zip

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Treatment ID:TR002971
Treatment Summary:All in vitro experiments were performed at least 3 times. Primary bone marrow macrophages (BMMs) were prepared as described. Marrow was extracted from femora and tibiae of 6- to 8-week-old mice with α minimum essential medium (α-MEM) and cultured in α-MEM containing 10% inactivated fetal bovine serum, 100 IU/mL penicillin, and 100 μg/mL streptomycin (α-10 medium) with 1:10 of mMCSF producing cell line, CMG 14-12 condition media on petri-plastic dishes. Cells were incubated at 37°C in 5% CO2 for 3 days and then washed with phosphate-buffered saline (PBS) and lifted with 1X trypsin/EDTA in PBS. A total of 1.2 × 104 BMMs were cultured in 500 μL α-MEM containing 10% heat-inactivated fetal bovine serum with glutathione-S transferase–RANKL and 30 ng/mL of mouse recombinant macrophage colony-stimulating factor (M-CSF) in 48-well tissue culture plates, some containing sterile bovine bone slices.