Research from Ono & Ono Lab published on bone-making, endosteal stem cells

Research from the Ono and Ono Laboratory at UTHealth Houston School of Dentistry on endosteal stem cells and their role in making bones has been published by Nature Communications.

Bone marrow is composed of blood cells and their supporting “stromal” cells. The latter contains various types of skeletal stem cells (SSCs) that are important for bone formation, which actively occurs when we are young. However, the identity of SSCs in young bone marrow and how these cells effectively generation bone-making osteoblasts to support active bone formation remains unclear.

“When we are young, our bones are strong because there are a lot of new bones being made each day,” said Noriaki Ono, DDS, PhD. “When we get older, our bones tend to become brittle because there are less bones being made each day. The question is, what is the stem cell that is responsible for very active and youthful bone formation?”

Through research, the laboratory found bone-making stem cells are different in young and adult bones and identified a new type of skeletal stem cells, called “endosteal stem cells,” which live in the bone marrow near the bone surface.

The Ono and Ono Laboratory found endosteal stem cells are particularly active in young bones but the activity decreases in the later stage of life.

Additionally, while endosteal stem cells make a lot of bones in normal conditions and regeneration, the researchers also found the cells can also turn into bone-tumor-making cells when they have detrimental mutations in tumor suppressor genes, which the authors noted may explain a high incidence of devastating bone cancer, osteosarcoma, in young populations.

The laboratory used genetically engineered models to perform in vivo lineage tracing. In this approach, a specific group of cells in the bone marrow can be permanently marked with fluorescent proteins, and the fate of these cells can be observed as bone formation progresses.

Cells marked by fluorescent proteins were analyzed using microscopes, and cells were also isolated for additional single-cell level molecular analyses to understand their gene expressions. Additionally, the laboratory specifically inactivated the P53 tumor suppressor gene in endosteal stem cells and analyzed how bone tumors developed.

In the next steps of the research, the Ono and Ono Laboratory plans to explore if endosteal stem cells can be a therapeutic target of bone diseases and their potential application in cell-based therapies.

Authors on the paper, titled “Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis,” included Yuki Matsushita, DDS, PhD, former postdoctoral research fellow, as the first author; Jialin Liu, MS, University of Michigan; Angel Ka Yan Chu, MS, University of Michigan; Chiaki Arai, DDS, PhD, research fellow; Mizuki Nagata, DDS, PhD, research fellow; Yuki Arai, research fellow; Wanida Ono, DDS, DMSc, PhD, associate professor; Kouhei Yamamoto, MD, PhD, Tokyo Medical and Dental University; Thomas Saunders, PhD, University of Michigan; Joshua Welch, PhD, University of Michigan; and Noriaki Ono, DDS, PhD, associate professor. The paper was published April 25.