CD47 is Required for Mesenchymal Progenitor Proliferation and Fracture Repair.

CD47 is a ubiquitous and pleiotropic cell-surface receptor. Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries. In a murine closed-fracture model, CD47-null mice showed decreased callus bone volume, bone mineral content, and tissue mineral content as assessed by microcomputed tomography 10 days post-fracture, and increased fibrous volume as determined by histology.

Inhibition of VEGFR2 Activation and Its Downstream Signaling to ERK1/2 and Calcium by Thrombospondin-1 (TSP1): Investigation.

VEGF signaling through VEGFR2 is a central regulator of the angiogenic response. Inhibition of VEGF signaling by the stress-induced matricellular protein TSP1 plays a role in modulating the angiogenic response to VEGF in both health and disease. TSP1 binding to CD47 inhibits VEGFR2 activation.

Thrombospondin-1/CD36 pathway contributes to bone marrow-derived angiogenic cell dysfunction in type 1 diabetes via Sonic hedgehog pathway suppression.

Refractory wounds in diabetic patients present a significant clinical problem. Sonic hedgehog (SHH), a morphogenic protein central to wound repair, is deficient in diabetes. Regulation of SHH in wound healing is poorly understood.

Nitric oxide and its gatekeeper thrombospondin-1 in tumor angiogenesis.

Nitric oxide (NO) plays a central role in angiogenesis as a mediator of signaling by vascular endothelial growth factor and other angiogenic factors. Low concentrations of NO produced in response to angiogenic factors stimulate angiogenesis, whereas higher concentrations typical of inflammatory responses inhibit angiogenesis. The proangiogenic activity of NO is mediated by activation of soluble guanylyl cyclase, leading to cyclic guanosine 3',5'-monophosphate accumulation and activation of its target kinases and ion channels.