DDR2, a discoidin domain receptor, is a marker of periosteal osteoblast and osteoblast progenitors
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ORIGINAL ARTICLE
DDR2, a discoidin domain receptor, is a marker of periosteal osteoblast and osteoblast progenitors Haili Yang1 · Lei Sun1 · Wenqian Cai1 · Jingkai Gu1 · Dacai Xu1,2 · Arjun Deb3 · Jinzhu Duan1 Received: 22 November 2019 / Accepted: 7 April 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020
Abstract Introduction 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. Results 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. Conclusion 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. Keywords Osteoblasts · DDR2 · FSP-1 · Periosteum · Alkaline phosphatase
Introduction
* Arjun Deb [email protected] * Jinzhu Duan [email protected] 1
Heart Center and Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9 JinSui Road, Guangzhou 510120, Guangdong, China
2
Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai 200031, China
3
Division of Cardiology, Department of Medicine, Department of Molecular Cell and Developmental Biology, UCLA Cardiovascular Medicine Research Theme, Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, 675 Charles E Young Drive S, MRL 3609, Los Angeles, CA 90095, USA
The periosteum is a dense bilayered connective tissue that surrounds cortical bone [1]. The inner layer of the periosteum, also known as the cambial layer, is rich in osteoblasts and osteoblast progenitors, while the outer layer of
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