A question of rotation

In mice, long bones have different ways of growing longer and wider before and after birth.

A 3D representation of chondrocytes arranged in a column after birth. Image credit: Sarah Rubin (CCBY 4.0)

As we develop, the long bones in our arms and legs must grow bigger and stronger to support our weight and movements. The width and length of these bones increase rapidly while in the womb, but after birth, they lengthen more quickly than they widen.

Both expansion and extension occur at the growth plates, two narrow zones located at each bone’s ends and which host cells that can divide and increase in size. Traditionally, bone lengthening has been understood resulting from these ‘chondrocytes’ expanding in size after having organized themselves into columns that run parallel to the long axis of the bone. This is possible due to newly born cells performing a complex 90-degree rotation that results in this characteristic organization in column stacks. How bones widen, however, is less well-understood.

To shed light on these mechanisms, Rubin, Agrawal et al. took advantage of recent technologies that allowed them to track the spatial organization of cells in 3D during development. Their experiments showed that, in mice, chondrocytes in the growth plate were rarely organized in columns before birth, with most cells not performing a 90-degree rotation of their division plane. This led to most clusters growing perpendicularly to the long axis of the bone, resulting in bone widening.

After birth, however, most chondrocytes successfully completed the rotation, establishing columns running parallel to the long axis; fewer clusters contributing to the widening of the bone were present.

Taken together, these results suggest that controlling the rotation of the division plane in chondrocytes helps create different growth strategies before and after birth. They also indicate that elongation in the womb may not require chondrocytes to be systematically organized in columns. Overall, the findings by Rubin, Agrawal et al. point to new mechanisms underpinning bone growth, which could be important to investigate further in both health and disease.