The purpose of this investigation was to evaluate the effects of bone morphogenetic protein-2 (BMP-2) and doxycycline on the in vitro differentiation of osteoprogenitor cells isolated from human femoral cancellous bone. The differentiation of osteoprogenitors into bone-forming osteoblasts was evaluated by alkaline phosphatase activity, osteocalcin gene expression, and the number of Von Kossa-positive bone nodules. Treatment of osteoprogenitors with BMP-2, at all concentrations tested, and doxycycline, at 10 and 50 µM, significantly increased the number of mineralized bone nodules and coincided with expression of osteocalcin. In conclusion, doxycycline at 10 and 50 µM had similar stimulatory osteoinductive effects as BMP-2 and could thus be considered as an alternative agent to BMP-2.