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



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.

Materials and methods

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.

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This work was supported by National Natural Science Foundation of China (NSFC#81670262), Guangzhou lingnan yingjie project and the start-up funding from Guangzhou Women and Children’s Medical Center and grants HL129178, HL137241, AR075867 from the National Institues of Health, and PR190268 and PR161247 from the Department of Defense, United states of America.

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HY performed most of the experiments and data analysis with LS, JG and DC, WQ, AD and JD designed the study and wrote the manuscript.

Corresponding authors

Correspondence to Arjun Deb or Jinzhu Duan.

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The authors report no conflict of interest.

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All animal studies were approved by the Institutional Animal Care and Use Committee of the Guangzhou Medical University (the acceptance number:2016-025) and all animal procedures conform to the National Institutes of Health (NIH) guidelines. This article does not contain any studies with human participants performed by any of the authors.

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Yang, H., Sun, L., Cai, W. et al. DDR2, a discoidin domain receptor, is a marker of periosteal osteoblast and osteoblast progenitors. J Bone Miner Metab 38, 670–677 (2020).

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  • Osteoblasts
  • DDR2
  • FSP-1
  • Periosteum
  • Alkaline phosphatase