Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow

► Using an enzymatic digestion approach, we separately isolated endosteal and central bone marrow from rodent long bones. ► The endosteal bone marrow contained a much higher number of mesenchymal progenitors than the central bone marrow. ► Endosteal mesenchymal progenitors are able to undergo multi-lineage differentiation and express mesenchymal stem cell surface markers. ► Endosteal mesenchymal progenitors are more proliferative, immunosuppressive, and responsive to aging and parathyroid hormone than central mesenchymal progenitors. ► Therefore, they represent a distinct population of mesenchymal progenitors that are more metabolically active and relevant to physiological bone formation.