CYR61 delivery promotes angiogenesis during bone fracture repair
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.
Authors
- Madhura P. Nijsure (ORCID: https://orcid.org/0000-0003-4268-9769)
- Annemarie Lang (ORCID: https://orcid.org/0000-0002-6539-9476)
- Christopher J. Panebianco (ORCID: https://orcid.org/0000-0001-8683-5743)
- Joel D. Boerckel (ORCID: https://orcid.org/0000-0003-3126-3025)
- Rui Tang (ORCID: https://orcid.org/0000-0002-3161-801X)
- Emily A. Eastburn
- Riccardo Gottardi (ORCID: https://orcid.org/0000-0001-8040-5531)
- Dongeun Huh (ORCID: https://orcid.org/0000-0002-5718-6884)
- Eben Alsberg (ORCID: https://orcid.org/0000-0002-3487-4625)
- Nick J. Willett (ORCID: https://orcid.org/0000-0003-3421-2549)
- Mousa Younesi
- Carly Siciliano
- Annapurna Pranatharthi Haran
- Elizabeth Seidl (ORCID: https://orcid.org/0009-0008-2652-2671)
Institutions
- Children's Hospital of Philadelphia (US)
- University of Oregon (US)
- University of Michigan (US)
- University of Illinois Chicago (US)
- Birmingham VA Medical Center (US)
- Jesse Brown VA Medical Center (US)
- VA Portland Health Care System (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- npj Regenerative Medicine
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1038/s41536-025-00398-y
- Citations
- 9
- Primary Topic
- Connective Tissue Growth Factor Research
- Type
- article
- Field-Weighted Citation Impact
- 7.25
Funders
- National Science Foundation
- Alternatives Research and Development Foundation
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of General Medical Sciences
- Division of Civil, Mechanical and Manufacturing Innovation