New Insights into bones

DRFZ colleagues from the research groups of Anja Hauser and Raluca Niesner have developed a new method enabling the cellular composition of entire bones to be visualised three-dimensionally using light sheet microscopy. This method was recently published in the journal Nature Communications.

Until now, it has been difficult to visualise whole bones with subcellular resolution due to their optical properties. The Hauser and Niesner research groups have now developed a method with which whole bones can be cleared, i.e. made transparent, in a mouse model. This allows their cellular composition to be analysed in 3D using light sheet microscopy.

Bones are not only the framework of our skeleton but are also involved in many rheumatic diseases. The bone marrow within bones is of great importance for the function of the immune system as it is the birthplace of blood cells and the location of the cellular immunological memory. The interaction of immune and stromal cells is of great importance in physiological, pathological and regenerative processes. A three-dimensional, spatially resolved analysis of the cellular relationships in bone and bone marrow is therefore crucial for our understanding of these processes.

In healthy bone marrow, age-related changes in the tissue structure were revealed using this novel method. For example, the size of the largest blood vessel, the central sinus, was found to decrease significantly in old mice. This could have important consequences for the exchange of blood cells from the bone marrow with the circulation.

The method also allowed the researchers to analyse the distribution of individual cells, for example CX₃CR1⁺ myeloid cells, in the bone during homeostasis and in the course of bone healing. While these cells are in close contact with blood vessels in healthy animals, a redistribution takes place after a bone injury, which leads to them demarcating the damaged tissue from the healthy tissue areas, enabling the sprouting of new blood vessels for regeneration.