The well-known matrix protein Dentin matrix protein 1 (DMP1) is expressed by osteoblasts and osteocytes in bone, and it controls bone mineralization. Recently, it has been found that DMPI is also expressed in other cell types, such as chondrocytes. Nestin(+) cells are one important type of progenitor cell in bone marrow and are associated with bone remodeling. In our preliminary experiment, DMP1 could also be detected in Nestin(+) cells in bone marrow. This study was designed to explore the effect on bone of DMPI in Nestin(+) cells. A transgenic mouse model with DMPI expression driven by the Nestin promoter was generated. In vivo and in vitro experiments revealed that overexpression of DMP1 in Nestin(+) cells could limit the proliferation and osteogenic differentiation of BMMSCs, subsequently leading to decreased bone mass. Lower expression of bone matrix protein and a lower bone deposition rate were also observed. Meanwhile, overexpression of DMP1 in Nestin(+) cells had no influence on osteoclast activity. These data indicate that DMP1 plays negative roles in differentiation of Nestin(+) cells and bone formation. (C) 2017 Elsevier Inc. All rights reserved.