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The tunica adventitia ensheathes arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells express the CD10/CALLA cell surface metalloprotease. Both CD10⁺ and CD10⁻ adventitial cells displayed phenotypic features of MSCs when expanded in culture. However, CD10⁺ adventitial cells exhibited higher proliferation, clonogenic and osteogenic potentials in comparison to their CD10⁻ counterparts. CD10⁺ adventitial cells increased expression of the cell cycle protein CCND2 via ERK1/2 signaling and osteoblastogenic gene expression via NF-κB signaling. CD10 expression was upregulated in adventitial cells through sonic hedgehog-mediated GLI1 signaling. These results suggest that CD10, which marks rapidly dividing cells in other normal and malignant cell lineages, plays a role in perivascular …