Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy.

Autor:	Yao L; Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, United States.; Department of Orthopaedics, The First Hospital of China Medical University, Shenyang, China., Lu J; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Zhong L; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Wei Y; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Gui T; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Wang L; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Ahn J; Department of Orthopaedic Surgery, Michigan Medicine, University of Michigan, Ann Arbor, United States., Boerckel JD; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Rux D; Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, United States., Mundy C; Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, United States., Qin L; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Pacifici M; Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Dec 11; Vol. 12. Date of Electronic Publication: 2023 Dec 11.
DOI:	10.7554/eLife.89822
Abstrakt:	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. Competing Interests: LY, JL, LZ, YW, TG, LW, JA, JB, DR, CM, LQ, MP No competing interests declared (© 2023, Yao et al.)
Databáze:	MEDLINE
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