New mechanism of bone growth uncovered.

It is known the growth of children’s bones depends on growth plates situated close to the end of all long bones in the body.  These plates are narrow discs of cartilage which provide a continuous supply of chondrocytes for bone formation.  However, it remains unknown how this supply is maintained throughout childhood growth.  Now, a study from researchers led by the Karolinska Institutet shows that bone growth in mice takes place in accordance with the same principles as when new cells are constantly produced in blood, skin and other tissue.  The team states this contradicts the established theory that bone growth depends on a finite number of gradually consumed progenitor cells.  The study is published in the journal Nature.

Previous  studies show chondrocytes form a kind of scaffold supporting the formation of new bone tissue, and are themselves generated from stem-cell like progenitor cells called chondroprogenitors. For long bones to grow properly, chondrocytes must be generated constantly throughout the  growth period. The general view in the field has been that there is a limited number of progenitor cells formed during embryonic development and consumed for bone growth until they run out and the person stops growing.  The current study investigates the formation of chondrocytes in mice to verify this fact.

The current study uses clonal genetic tracing in mice to demonstrate small ‘clones’ of cells are generated from the same progenitor cells during embryonic development, which is in line with the current view. Results show, however, after birth there are dramatic changes in cell dynamics and large, stable clones are formed because chondroprogenitors acquire the ability to regenerate.  Data findings show there is a stem cell niche in growth plates, and that bone growth ceases if this local micro-environment is disrupted, implying that bone growth in mice follows a completely different principle to what was once thought.

The team state that this progenitor cell behaviour is typical for tissue which constantly produces many new cells, such as skin, blood and intestine. They go on to explain that for these tissue types progenitor cells are known to be situated in a very specific micro-environment, a stem cell niche, which helps to generate the necessary cells and also enables the progenitor cells to renew themselves; if the niche is disrupted or dysfunctional, the progenitor cells become depleted and the tissue is damaged.

The team surmise they have identified a new mechanism of bone growth, namely a stem cell niche which develops postnatally in the growth plate, providing a continuous supply of chondrocytes over a prolonged period.  For the future, the researchers state if their findings also apply to humans, they could make an important contribution to the treatment of children with growth disorders.

Source: Karolinska Institutet


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