Work

CYR61 delivery promotes angiogenesis during bone fracture repair

Year: 2025

Type: article

Abstract: 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 has been implicated in 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.

Source: npj Regenerative Medicine

DOI: 10.1038/s41536-025-00398-y

Authors: Annemarie Lang, Emily A. Eastburn, Mousa Younesi, Madhura P. Nijsure, Carly Siciliano, Annapurna Pranatharthi Haran, Christopher J. Panebianco, Elizabeth Seidl, Rui Tang, Eben Alsberg, Nick J. Willett, Riccardo Gottardi, Dongeun Huh, Joel D. Boerckel

Institutions: University of Michigan, University of Pennsylvania, University of Illinois Chicago, Jesse Brown VA Medical Center, University of Oregon, VA Portland Health Care System, Children's Hospital of Philadelphia

Language: English

Topic: Connective Tissue Growth Factor Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,190

Funders: National Science Foundation, U.S. Department of Health and Human Services, Alternatives Research and Development Foundation, Deutsche Forschungsgemeinschaft, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Civil, Mechanical and Manufacturing Innovation, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Awards: G1199548893, IRACDA at the University of Pennsylvania: Penn Postdoctoral Opportunities in Research and Teaching (PennPORT)., G1590547780, G1870677656, G2290284674, Mechanical regulation of endochondral bone regeneration, G4481177325, G559906455, G5971055927, Osteoprogenitor mobilization for bone development and repair, G6392007099, G6440909772, G6717099065, G6963459767, G8373421954, G9000012673, G9000143702, Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application), Science and Technology Center for Engineering Mechano-Biology

OpenAlex ID: W4409665989

FWCI: 3.275

Cites: 72

Cited by: 13

Related to: 10