Bone marrow is in most big bones and makes billions of blood cells every day. But first, the body must make space in the bones for the marrow. Long bones start as solid and must be hollowed out. Without this, marrow cannot grow.

Osteoclasts are the cells that break down cartilage and bone to make room. They need a special protein called RANKL to work. Without RANKL, osteoclasts do not develop, and the marrow space does not form correctly.

A study from Japan found that bone marrow formation happens in two steps with two groups of cells. One group starts the hollowing process, and the other group expands and keeps the marrow space.

The researchers used special mice to track the cells that make RANKL. They used a technique to read the genetic activity of individual cells and track the cells over time.

The first cells that make RANKL come from the tissue around the cartilage and move towards the bone.

These cells are a new type of connective tissue cell. They help make osteoclasts and later become septoclasts, which dissolve cartilage. If RANKL is removed from these cells, osteoclast numbers decrease, and the marrow space is not made correctly.

A professor said that a special group of cells may trigger the formation of the bone marrow space, like how other cells initiate lymph node formation.

As the fetus develops, the first group of cells disappears, and another group takes over to keep the osteoclasts active. This second group of cells comes from progenitors that emerge later.

The study also found that the same sequence of cells happens when bones heal after a break. The cells that help make the marrow space also help heal bones.

The findings can help with bone diseases like osteoporosis and rheumatoid arthritis. Targeting the cells that control osteoclasts could be a new way to treat these diseases.

The study provides new information about bone marrow formation.

The research was done at Kyushu University.