The role of proteoglycan form of DMP1 in cranial repair

Abstract

Background The cranial region is a complex set of blood vessels, cartilage, nerves and soft tissues. The reconstruction of cranial defects caused by trauma, congenital defects and surgical procedures presents clinical challenges. Our previous data showed that deficiency of the proteoglycan (PG) form of dentin matrix protein 1 (DMP1-PG) could lead to abnormal cranial development. In addition, DMP1-PG was highly expressed in the cranial defect areas. The present study aimed to investigate the potential role of DMP1-PG in intramembranous ossification in cranial defect repair. Methods Mouse cranial defect models were established by using wild- type (WT) and DMP1-PG point mutation mice. Microcomputed tomography (micro-CT) and histological staining were performed to assess the extent of repair. Immunofluorescence assays and real-time quantitative polymerase chain reaction (RT‒qPCR) were applied to detect the differentially expressed osteogenic markers. RNA sequencing was performed to probe the molecular mechanism of DMP1-PG in regulating defect healing. Results A delayed healing process and an abnormal osteogenic capacity of primary osteoblasts were observed in DMP1-PG point mutation mice. Furthermore, impaired inflammatory signaling pathways were detected by using RNA transcription analysis of this model. Conclusions Our data indicate that DMP1-PG is an indispensable positive regulator during cranial defect healing.