Summary of project PR001784
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001784 |
| Project DOI: | doi: 10.21228/M83T50 |
| Project Title: | Bap1 Promotes Osteoclast Function by Metabolic Reprogramming |
| Project Type: | Untargeted Metabolomics |
| Project Summary: | Treatment 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. |
| Institute: | Washington University in St. Louis |
| Department: | Pathology and Immunology, Medicine, Chemistry |
| Laboratory: | Teitelbaum and Patti Laboratories |
| Last Name: | Cho |
| First Name: | Kevin |
| Address: | 1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA |
| Email: | kevin.cho@wustl.edu |
| Phone: | 314-935-8813 |
Summary of all studies in project PR001784
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002850 | Bap1 Promotes Osteoclast Function by Metabolic Reprogramming | Homo sapiens | Washington University in St. Louis | MS* | 2023-09-11 | 1 | 20 | Uploaded data (64.8M)* |
