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| Status |
Public on Jan 11, 2024 |
| Title |
Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Bone fraction healing is effective in most individuals, but can be subpar and not easily treatable in patients such as the elderly, requiring new remedies. Here we tested whether activin A promotes fracture repair, inspired by recent studies showing that the protein stimulates ectopic bone formation in other systems. Using a standard mouse tibia fracture model, we found that activin A became very abundant in the developing callus soon after fracture. Single cell RNA-seq and immunostaining showed that initially, expression of the activin A-encoding gene Inhba characterized inflammatory cells and periosteal mesenchymal lineage cells. Over time, Inhba expression became prominent in a unique, highly-proliferative progenitor cell (PPC) population that displayed a myofibroblast character and was at the center of a developmental trajectory bifurcation toward cartilage and bone cells in callus. Systemic administration of a neutralizing activin A monoclonal antibody delayed fracture healing, whereas local implantation of recombinant activin A enhanced it. Cells engaged in healing produced phosphorylated SMAD2 through which activin A normally signals intracellularly, and were also positive for aSMA, a recognized marker of myofibroblasts. In vitro gain- and loss-of-function assays showed that activin A directly stimulated chondrogenesis, osteogenesis and myofibroblast differentiation in periosteal progenitors. Our study reveals that activin A is a positive regulator of fracture repair and may represent a new therapeutic tool to enhance it. Its action involves a prominent and transient PPC population with a myofibroblastic character that would rapidly gear up to bring about repair in a timely and effective manner.
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| Overall design |
mesenchymal cell atlas during fracture healing process
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38079220/
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| Contributor(s) |
Yao L, Qin L, Pacifici M |
| Citation(s) |
38079220 |
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| Submission date |
Dec 27, 2021 |
| Last update date |
Jan 12, 2024 |
| Contact name |
Lutian Yao |
| E-mail(s) |
ltyao@cmu.edu.cn
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| Organization name |
the First Affiliated Hospital of China Medical University
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| Department |
Department of Orthopedic
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| Street address |
155 Nanjing st
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| City |
Shenyang |
| ZIP/Postal code |
110001 |
| Country |
China |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA792499 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE192630_RAW.tar |
343.2 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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