Mechanical loading regulates organization of the actin cytoskeleton and column formation in postnatal growth plate

Abstract

Longitudinal growth of bones occurs at the growth plates where chondrocytes align into columns that allow directional growth. Little is known about the mechanisms controlling the ability of chondrocytes to form columns. We hypothesize that mechanical load and the resulting force on chondrocytes are necessary during active growth for proper growth plate development and limb length. To test this hypothesis, we created a mouse model in which a portion of the sciatic nerve from one hind limb was transected at postnatal day 8 to cause paralysis to that limb. At 6 and 12 wk postsurgery, the hind limb had significantly less bone mineral density than contralateral controls, confirming reduced load. At 8 and 14 wk postsurgery, tibiae were significantly shorter than controls. The paralyzed growth plate showed disruptions to column organization, with fewer and shorter columns. Polarized light microscopy indicated alterations in collagen fiber organization in the growth plate. Furthermore, organization of the actin cytoskeleton in growth plate chondrocytes was disrupted. We conclude that mechanical load and force on chondrocytes within the growth plate regulate postnatal development of the long bones.