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 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

bioRxiv : the preprint server for biology - (2024) vom: 06. Apr.

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Preprint

Anmerkungen:

Date Revised 25.04.2024

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1101/2024.04.05.588239

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM37106533X