Research from Ono & Ono Lab published on perichondrial cells

Research from the Ono and Ono Laboratory at UTHealth Houston School of Dentistry on perichondrial cells and how they organize bone development has been published by Nature Communications.

Even the strongest bone begins with a tiny primordium (or anlage or template) that is formed during the fetal stage. In long bones, this primordium is comprised of two distinct tissues—the cartilage composed of chondrocytes and its surrounding perichondrium composed of fibroblastic cells. When bones grow bigger and stronger, this primordium disappears and turns into bone-making cells.

“Cells from the two sources—cartilage and its perichondrium—are important for bone development,” said Noriaki Ono, DDS, PhD. “However, it has not been known what types of cells they eventually become in fully grown bones. Many types of cells are there in the bone marrow, including osteoblasts and marrow adipocytes, and support the complex function of the bone.”

Through their research, the Ono and Ono Laboratory found that cells in the perichondrium are fated to become dormant adipocyte-like marrow stromal cells in a specific location of bone called the diaphysis. Therefore, cells in big bones are already pre-programmed long before birth in the fetal stage, within the two cells types that exist in the bone primordium.

The laboratory used genetically engineered models to perform the approach called in vivo lineage-tracing experiments. In this approach, a specific group of cells in the bone primordium were permanently marked with fluorescent proteins (red or green) to observe where these cells eventually go during bone development.

The fluorescently marked cells were analyzed using microscopes or by isolating these cells for additional single-cell level molecular analyses to understand their gene expressions. A specific signaling pathway (Hedgehog signaling) in a specific group of cells were also manipulated to analyze the impact on bone shapes.

Through their research, the Ono and Ono Laboratory found early perichondrial cells of the bone primordium in the fetal stage (expressing Dlx5) are destined to become dormant adipocyte-like stromal cells, while fetal chondrocytes (expressing Fgfr3) are fated to become more active osteoblast/chondrocyte-like cells in the bone marrow. This means the diversity of cells in fully grown bones is already determined in the fetal primordial stage.

“The findings from our study will provide the fundamental knowledge for understanding how a variety of congenital bone deformities arise during bone development due to deficiencies in these two types of cells, and possibly provide potential therapeutic targets,” Ono said. “The next step will be to understand how early perichondrial cells that we identified in our study are involved in a variety of pediatric bone diseases, and if these cells can be a potential therapeutic target of repairing bone deformities.”

Authors on the paper, titled “The fate of early perichondrial cells in developing bones,” included Yuki Matsushita, DDS, PhD, former postdoctoral research fellow, as the first author; Chiaki Arai, DDS, PhD, research fellow; Shion Orikasa, DDS, PhD, research fellow; Mizuki Nagata, DDS, PhD, research fellow; Wanida Ono, DDS, DMSc, PhD, associate professor; and Noriaki Ono, DDS, PhD, associate professor. The paper was published Nov. 28.