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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.gene.2023.147481 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A preliminary study of cell-based bone tissue engineering into 3D-printed β-tricalcium phosphate scaffolds and polydioxanone membranes.
Sci Rep
December 2024
Department of Basic Sciences, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, 16066-840, Brazil.
Treatment of complex craniofacial deformities is still a challenge for medicine and dentistry because few approach therapies are available on the market that allow rehabilitation using 3D-printed medical devices. Thus, this study aims to create a scaffold with a morphology that simulates bone tissue, able to create a favorable environment for the development and differentiation of osteogenic cells. Moreover, its association with Plenum Guide, through cell-based tissue engineering (ASCs) for guided bone regeneration in critical rat calvarial defects.
View Article and Find Full Text PDFMechanism of Interleukin-17A Regulation of Mesenchymal Stroma/Stem Cell Osteogenic Differentiation.
Discov Med
December 2024
Department of Molecular Oncology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
The immune and musculoskeletal systems closely interplay in bone repair and regeneration. After bone injury, the body produces high levels of cytokines and signaling molecules to balance bone formation and resorption. Interleukin (IL)-17A, a cytokine expressed early in the inflammatory process, profoundly influences osteoprogenitor cell fate, thereby contributing to bone homeostasis.
View Article and Find Full Text PDFCCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice.
J Cell Mol Med
December 2024
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
Macrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage-associated CCL2 secretion, its influence on mesenchymal stem/progenitor cell (MSPC) chemotaxis, and in vivo cell recruitment using Ccr2 (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre-osteoblasts, MSPC) upregulated CCL2.
View Article and Find Full Text PDFEffective Bone Tissue Fabrication Using 3D-Printed Citrate-Based Nanocomposite Scaffolds Laden with BMP9-Stimulated Human Urine Stem Cells.
ACS Appl Mater Interfaces
December 2024
Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center; Chicago, Illinois 60637, United States.
Effective repair of large bone defects through bone tissue engineering (BTE) remains an unmet clinical challenge. Successful BTE requires optimal and synergistic interactions among biocompatible scaffolds, osteogenic factors, and osteoprogenitors to form a highly vascularized microenvironment for bone regeneration and osseointegration. We sought to develop a highly effective BTE system by using 3D printed citrate-based mPOC/hydroxyapatite (HA) composites laden with BMP9-stimulated human urine stem cells (USCs).
View Article and Find Full Text PDFRejuvenating aged osteoprogenitors for bone repair.
Elife
December 2024
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Aging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!