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- Title
Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy.
- Authors
Lutian Yao; Jiawei Lu; Leilei Zhong; Yulong Wei; Tao Gui; Luqiang Wang; Ahn, Jaimo; Boerckel, Joel D.; Rux, Danielle; Mundy, Christina; Ling Qin; Pacifici, Maurizio
- Abstract
Insufficient bone fracture repair represents a major clinical and societal burden and novel strategies are needed to address it. Our data reveal that the transforming growth factor-β superfamily member Activin A became very abundant during mouse and human bone fracture healing but was minimally detectable in intact bones. Single-cell RNA-sequencing revealed that the Activin A-encoding gene Inhba was highly expressed in a unique, highly proliferative progenitor cell (PPC) population with a myofibroblast character that quickly emerged after fracture and represented the center of a developmental trajectory bifurcation producing cartilage and bone cells within callus. Systemic administration of neutralizing Activin A antibody inhibited bone healing. In contrast, a single recombinant Activin A implantation at fracture site in young and aged mice boosted: PPC numbers; phosphorylated SMAD2 signaling levels; and bone repair and mechanical properties in endochondral and intramembranous healing models. Activin A directly stimulated myofibroblastic differentiation, chondrogenesis and osteogenesis in periosteal mesenchymal progenitor culture. Our data identify a distinct population of Activin A-expressing PPCs central to fracture healing and establish Activin A as a potential new therapeutic tool.
- Subjects
FRACTURE healing; BONE mechanics; PROGENITOR cells; CELL populations; ACTIVIN; BONE regeneration; CARTILAGE cells; BONE fractures
- Publication
eLife, 2024, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.89822