Cyr61 delivery promotes angiogenesis during bone fracture repair.

Autor:	Lang A; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States., Eastburn EA; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Younesi M; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Nijsure M; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Siciliano C; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Haran AP; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Panebianco CJ; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States., Seidl E; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Tang R; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, United States., Alsberg E; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, United States., Willett NJ; Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR, United States.; The Veterans Affairs Portland Health Care System, Portland, OR, United States., Gottardi R; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.; Children's Hospital of Philadelphia, Philadelphia, PA, United States., Huh D; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States., Boerckel JD; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 06. Date of Electronic Publication: 2024 Apr 06.
DOI:	10.1101/2024.04.05.588239
Abstrakt:	Compromised vascular supply and insufficient neovascularization impede bone repair, increasing risk of non-union. Cyr61, Cysteine-rich angiogenic inducer of 61kD (also known as CCN1), is a matricellular growth factor that is regulated by mechanical cues during fracture repair. Here, we map the distribution of endogenous Cyr61 during bone repair and evaluate the effects of recombinant Cyr61 delivery on vascularized bone regeneration. In vitro, Cyr61 treatment did not alter chondrogenesis or osteogenic gene expression, but significantly enhanced angiogenesis. In a mouse femoral fracture model, Cyr61 delivery did not alter cartilage or bone formation, but accelerated neovascularization during fracture repair. Early initiation of ambulatory mechanical loading disrupted Cyr61-induced neovascularization. Together, these data indicate that Cyr61 delivery can enhance angiogenesis during bone repair, particularly for fractures with stable fixation, and may have therapeutic potential for fractures with limited blood vessel supply. Competing Interests: Competing interests: Authors declare that they have no competing interests.
Databáze:	MEDLINE
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