Summary of Study ST002850
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
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.
| Study ID | ST002850 |
| Study Title | Bap1 Promotes Osteoclast Function by Metabolic Reprogramming |
| Study Type | Untargeted Metabolomics |
| Study 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 |
| kevin.cho@wustl.edu | |
| Phone | 314-935-8813 |
| Submit Date | 2023-08-26 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-09-11 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004668 | AN004669 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Vanquish Flex UHPLC Systems | Thermo Vanquish Flex UHPLC Systems |
| Column | HILICON iHILIC-(P) Classic (100 x 2.1mm,5um) | HILICON iHILIC-(P) Classic (100 x 2.1mm,5um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Orbitrap ID-X tribrid | Thermo Orbitrap ID-X tribrid |
| Ion Mode | NEGATIVE | POSITIVE |
| Units | peak area | peak area |
MS:
| MS ID: | MS004415 |
| Analysis ID: | AN004668 |
| Instrument Name: | Thermo Orbitrap ID-X tribrid |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Data were collected with the following MS source settings: spray voltage, -2.8 kV; sheath gas, 50; auxiliary gas, 10; sweep gas, 1; ion transfer tube temperature, 300°C; vaporizer temperature, 200°C; mass range, 67 – 1000 Da; resolution, 120,000; maximum injection time, 200 ms; isolation window, 1.5 Da. XCMS and Skyline software were used for data processing |
| Ion Mode: | NEGATIVE |
| MS ID: | MS004416 |
| Analysis ID: | AN004669 |
| Instrument Name: | Thermo Orbitrap ID-X tribrid |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Data were collected with the following MS source settings: spray voltage, 3.5 kV; sheath gas, 50; auxiliary gas, 10; sweep gas, 1; ion transfer tube temperature, 300°C; vaporizer temperature, 200°C; mass range, 67 – 1000 Da; resolution, 120,000; maximum injection time, 200 ms; isolation window, 1.5 Da. XCMS and Skyline software were used for data processing |
| Ion Mode: | POSITIVE |
