DDR2, a discoidin domain receptor, is a marker of periosteal osteoblast and osteoblast progenitors

• DOI: 10.1007/s00774-020-01108-y
• Publication Date: 2020-05-15T12:04:01Z
• Authors: Haili Yang; Lei Sun; Wenqian Cai; Jingkai Gu; Dacai Xu; Arjun Deb; Jinzhu Duan
• Keywords: Clinical Sciences; Clinical sciences; Regenerative Medicine; Inbred C57BL; Calcification; Paediatrics and Reproductive Medicine; Mice; Endocrinology & Metabolism; 03 medical and health sciences; Calcification, Physiologic; Osteogenesis; Periosteum; Alkaline phosphatase; 2.1 Biological and endogenous factors; DDR2; Animals; S100 Calcium-Binding Protein A4; Aetiology; Physiologic; Discoidin Domain Receptors; 0303 health sciences; Osteoblasts; Biomedical and Clinical Sciences; Cell Differentiation; Stem Cell Research; Alkaline Phosphatase; Mice, Inbred C57BL; FSP-1; Osteoporosis; Stem Cell Research - Nonembryonic - Non-Human; Biochemistry and Cell Biology; Biomarkers

The periosteum has a bilayered structure that surrounds cortical bone. The outer layer is rich in connective tissue and fibroblasts, while the inner layer in contact with the cortical surface of the bone predominantly consists of osteoblasts and osteoblast progenitors. The identification of cell-specific surface markers of the bilayered structure of the periosteum is important for the purpose of tissue regeneration.We investigated the expression of the discoidin domain tyrosine kinase receptor DDR2, fibroblast specific protein-1 (FSP-1) and alkaline phosphatase (ALP) in the periosteum of cortical bone by immunohistochemistry. Osteogenic differentiation was compared between DDR2- and FSP-1-expressing cells flow-sorted from the periosteum.We showed that DDR2 predominantly labeled osteogenic cells residing in the inner layer of the periosteum and that Pearson's coefficient of colocalization indicated a significant correlation with the expression of ALP. The mineralization of DDR2-expressing osteogenic cells isolated from the periosteum was significantly induced. In contrast, FSP-1 predominantly labeled the outer layer of periosteal fibroblasts, and Pearson's coefficient of colocalization indicated that FSP-1 was poorly correlated with the expression of DDR2 and ALP. FSP-1-expressing periosteal fibroblasts did not exhibit osteogenic differentiation for the induction of bone mineralization.DDR2 is a novel potential cell surface marker for identifying and isolating osteoblasts and osteoblast progenitors within the periosteum that can be used for musculoskeletal regenerative therapies.