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Molecular profiling of osteoprogenitor cells reveals FOS as a master regulator of bone non-union [timecourse]

ABSTRACT: Despite the advances in bone fracture treatment, a significant fraction of fracture patients will develop non-union. Most non-unions are treated with surgery since identifying the molecular causes of these defects is exceptionally challenging. In this study, compared with marrow bone, we generated a transcriptional atlas of human osteoprogenitor cells derived from healing callus and non-union fractures. Detailed comparison among the three conditions revealed a substantial similarity of callus and nonunion at the gene expression level. Nevertheless, when assayed functionally, they showed different osteogenic potential. Utilizing longitudinal transcriptional profiling of the osteoprogenitor cells, we identified FOS as a putative master regulator of non-union fractures. We validated FOS activity by profiling a validation cohort of 31 tissue samples. Our work identified new molecular targets for non-union classification and treatment while providing a valuable resource to better understand human bone healing biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226565 | GEO | 2024/01/10

REPOSITORIES: GEO

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Molecular profiling of osteoprogenitor cells reveals FOS as a master regulator of bone non-union [tissue]

Project description:Despite the advances in bone fracture treatment, a significant fraction of fracture patients will develop non-union. Most non-unions are treated with surgery since identifying the molecular causes of these defects is exceptionally challenging. In this study, compared with marrow bone, we generated a transcriptional atlas of human osteoprogenitor cells derived from healing callus and non-union fractures. Detailed comparison among the three conditions revealed a substantial similarity of callus and nonunion at the gene expression level. Nevertheless, when assayed functionally, they showed different osteogenic potential. Utilizing longitudinal transcriptional profiling of the osteoprogenitor cells, we identified FOS as a putative master regulator of non-union fractures. We validated FOS activity by profiling a validation cohort of 31 tissue samples. Our work identified new molecular targets for non-union classification and treatment while providing a valuable resource to better understand human bone healing biology.

2024-01-10 | GSE226566 | GEO

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Molecular profiling of osteoprogenitor cells reveals FOS as a master regulator of bone non-union

Project description:Molecular profiling of osteoprogenitor cells reveals FOS as a master regulator of bone non-union

| PRJNA940702 | ENA

Transcription profiling of femoral fracture healing in Rattus norvegicus subjects comparing intramedullary nailing, screw and plate fixation, and sham surgery

Project description:This is a study of femoral fracture healing in female rats 16 weeks old at fracture to compare intramedullary nailing, screw and plate fixation, and sham surgery. The sham surgery group received a surgical exposure of the femur, but no fracture, no plate, and no nail. Samples were collected at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery. Each sample is a pool of RNA from three rats from the same surgery group at the same time point after fracture. The middle third of the femur was collected with the cortical bone, fracture callus, and marrow elements. Mid-diaphyseal, simple, transverse fractures were induced by a Gigli saw. The no fracture sample was a time 0 control collected on the day of surgery from intact rats.

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Fracture healing in osteoporotic mice

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