Spatial mapping of growth plate tissue may help explain how bones grow

Researchers at the Department of Women's and Children's Health have employed a cutting-edge method known as spatial transcriptomics to map gene activity within the growth plates of human skeletons. This technique allowed them to identify which genes were switched on in various regions of the growth plates. The findings shed new light on the regulatory processes behind bone elongation and why certain genetic mutations result in skeletal disorders.

The study's results, published in the journal Bone Research, suggest that the mechanisms governing growth maintenance remain largely elusive. Growth plates in the skeleton play a crucial role in determining adult height during childhood and adolescence. However, the precise mechanisms governing growth maintenance are still not fully understood.

In their research, scientists examined minute samples of human growth plate tissue using spatial transcriptomics, a technique that reveals the specific locations of active genes within the tissue sample. One particular area of interest is the resting zone of the growth plate, which comprises cells with stem cell-like properties, often referred to as quiescent or hibernating cells.

Phillip Newton, a docent at the Department of Women's and Children's Health, explained that these cells were found to display more genetic and functional differences than previously anticipated. The researchers also pinpointed a range of genes active in the growth plate, including the SGMS2 gene, which was discovered to be expressed in cartilage cells responsible for mineralization within the tissue.

Minerslization takes place in tiny structures called matrix vesicles, and the researchers found that the protein produced by SGMS2 is present within these structures in mice. When the protein's activity was experimentally inhibited, mineral formation was compromised, which could explain why mutations in the SGMS2 gene in humans lead to a rickets-like disorder characterized by improper mineralization of the skeleton.

The discovery of both well-established and novel gene activities within the growth plate strengthens prior research conducted using model organisms and cell-based systems, while also identifying potential new causes of growth disorders. The heterogeneous nature of cells within the resting zone implies that growth regulation is more intricate than previously assumed.

A lingering question for future research is whether growth is driven by a single type of stem cell or by a diverse pool of equipotent progenitor cells. As spatial transcriptomic technologies continue to evolve, researchers anticipate the ability to map cellular states with even greater precision, providing deeper insights into the regulation of skeletal growth.