The regeneration of bone defects is necessary for the successful healing. During the process of healing, callus plays crucial roles in providing the stable bone-reconstruction environment. The callus is consisted of various large molecules including collagen proteins, non-collagen proteins and proteoglycans (PGs), which are involved in maintaining mechanical strength and interacting with cytokines and grow factors in the injury sites. Recently, our data have found that the PG form of Dentin Matrix Protein 1 (DMP1-PG), which is a newly identified PG, was richly expressed in the bone defect sites. Previous researches have demonstrated the special role of DMP1-PG in chondrogenesis and endochondral ossification, however, the knowledge about the role of DMP1-PG in bone defect repair is still limited. To further detect the potential function of DMP1-PG in the defect healing, we employed a bone defect intramembranous ossification model using the glycosylation site mutant DMP1-PG (S-89-G(89), S89G-DMP1) mouse. The morphologic changes of calluses and abnormal expression levels of osteogenesis genes were displayed in the injury sites in S89G-DMP1 mice. In addition, impaired BMP-Smad signaling pathway was observed due to the deficiency of DMP1-PG. Collectively, our findings indicated that the DMP1-PG is one of key proteoglycans in the process of defect healing via regulating the osteogenesis. (C) 2020 Elsevier Inc. All rights reserved.