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Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis

  A research group led by Associate Professor Yuki Matsushita of Nagasaki University Graduate School of Biomedical Sciences and Dr. Noriaki Ono of the University of Texas conducted international joint research with the University of Michigan in the United States. As a result, they discovered new bone stem cells in bone marrow, which had not been identified yet, and named “Endosteal Stem Cells.” The research revealed that these new stem cells contribute to bone growth and regeneration and may also be the origin of cancer.
The research was published in “Nature Communications” on April 25, 2023.

■Research Abstract:
The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR)+ perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear. Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 (Fgfr3) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. These Fgfr3-creER-marked endosteal stromal cells contribute to a stem cell fraction in young stages, which is later replaced by Lepr-cre-marked stromal cells in adult stages. Further, Fgfr3+ endosteal stromal cells give rise to aggressive osteosarcoma-like lesions upon loss of p53 tumor suppressor through unregulated self-renewal and aberrant osteogenic fates. Therefore, Fgfr3+ endosteal SSCs are abundant in young bone marrow and provide a robust source of osteoblasts, contributing to both normal and aberrant osteogenesis.

■Journal information 
Title:Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis
Author information:Yuki Matsushita1,2#, Jialin Liu3#, Angel Ka Yan Chu3, Chiaki Tsutsumi-Arai1, Mizuki Nagata1, Yuki Arai1, Wanida Ono1, Naoko Sakagami1, Kouhei Yamamoto4, Thomas L. Saunders5, Joshua D. Welch3*, Noriaki Ono1*

# First author
* Corresponding author
1. University of Texas Health Science Center at Houston School of Dentistry
2. Department of Cell Biology, Nagasaki University Graduate School of Biomedical Sciences
3. Department of Computational Medicine and Bioinformatics, University of Michigan
4. Department of Comprehensive Pathology, Tokyo Medical and Dental University
5. Transgenic Animal Model Core, University of Michigan Medical School

Journal: Nature Communications

This release is also available in Japanese.