Unraveling CD47's role in bone fracture healing

Bone fracture healing is a highly coordinated process involving inflammation, fibrovascular formation, and mineralization. Vascularization plays a pivotal role, as inadequate blood supply can severely hinder healing. CD47, a protein present on nearly all human cells, has been linked to tissue regeneration and blood vessel formation. While previous research indicated that disrupting CD47 could enhance soft tissue repair, its function in bone healing remained a mystery. Given the challenges associated with bone regeneration, understanding CD47's specific role became a pressing scientific question.

Published (DOI: 10.1038/s41413-025-00409-0) on March 3, 2025, in Bone Research, a study led by researchers from the University of Michigan and collaborating institutions delves into this mystery. Using murine models, the team found that mice lacking CD47 exhibited delayed callus formation and significantly lower bone volume compared to their wild-type counterparts. The findings underscored CD47's essential role in MSC proliferation, a critical factor for effective bone repair.

To investigate the impact of CD47 deficiency, the researchers employed a murine closed-fracture model and used advanced imaging techniques such as microcomputed tomography (μCT) and histomorphometric analysis. The results were striking—CD47-null mice exhibited markedly reduced callus formation and lower bone volume at 10 days post-fracture, accompanied by an increase in fibrous tissue. However, by day 20, the differences diminished, suggesting that CD47 primarily influences the early stages of healing.

Further in vitro experiments revealed that CD47-deficient MSCs demonstrated reduced colony formation and impaired proliferation, despite maintaining normal osteoblast differentiation. This indicates that CD47 is vital for MSC expansion, ensuring a sufficient supply of precursor cells for bone regeneration. Additionally, while endothelial cells lacking CD47 displayed increased proliferation—consistent with previous research—this was insufficient to compensate for the compromised MSC function.

The study also examined the effects of CD47 disruption in ischemic fracture models, where blood flow is severely restricted. Here, the absence of CD47 led to even smaller callus volumes and decreased bone mineral content, reinforcing its importance in healing under impaired vascular conditions.

Our findings reveal a dual role for CD47 in bone healing. While CD47 supports mesenchymal progenitor cell proliferation, its absence paradoxically promotes endothelial cell growth. This delicate balance is key to effective fracture repair, and targeting CD47 presents a promising avenue for enhancing bone healing, particularly in patients with vascular deficiencies."

Dr. Kurt D. Hankenson, senior author of the study

The implications of these findings extend far beyond basic science. For individuals with conditions such as diabetes or peripheral artery disease—where fracture healing is often impaired—modulating CD47 could provide a much-needed therapeutic breakthrough. Future studies will focus on harnessing CD47-targeting strategies, such as inhibitors or activators, to enhance MSC function and accelerate fracture recovery. This research not only advances our understanding of bone biology but also opens new doors for exploring CD47's broader role in tissue regeneration and vascular health.