Born to move: Development of form and function of the locomotor system in the early juvenile phase of precocial animals

Abstract

Precocial animals are extraordinary creatures, as they are able to walk within an hour after birth. However, hardly any information regarding the early development of gait in the horse was available. Also the ways the precocial skeleton copes with the sudden changes in loading after birth were largely unexplored. Therefore, the main aims of this thesis were to investigate the early development of gait in the foal and relate this to the (development of the) trabecular and subchondral bone of the distal tibia and talus in order to investigate how the skeleton prepares for postnatal loading. During growth, the foal’s preferred speed increases due to increased limb length and larger stride length. Meanwhile, relative limb loading remains fairly constant. Gait and balance need time to mature, characterised by a reduction of variability of stance duration and pressure distribution under the hooves. Clinical signs associated with osteochondrosis were not observed, however there was radiographic presence of OC in some animals, which led to a temporary, but significant, reduction in loading of the affected limb. Micro-CT imaging of trabecular bone of calves and foals revealed that foals rely on a relatively high bone volume fraction to anticipate postnatal loading. In calves the trabecular bone volume fraction is lower, but trabeculae are more aligned. These differences are likely related to species-related differences in anatomy. Surprisingly, Shetland pony bone was characterised by a higher bone volume fraction than in warmblood foals, possibly related to differences in growth rate. During growth, equine trabecular bone volume fraction of the distal tibia and talus increases due to increasing trabecular thickness. However, no significant changes in trabecular orientation and alignment were found. Similarly, collagen content increased significantly, but the degree of anisotropy of the collagen type I network did not, providing further evidence for prenatal anticipatory bone development in the horse. Prostaglandins are known to play important roles during bone growth and homeostasis, suggesting that suppression of prostaglandin production might have a negative effect. However, we did not observe adverse effects on skeletal development after the long-term administration of the regular dose of the COX-2 inhibitor meloxicam in growing pigs. Therefore, the drug might be helpful for treating pigs that are in pain, thus improving welfare. The osteoclast is a multinucleated cell responsible for resorption of bone and of key importance for bone remodelling. Cellular senescence is essential for tissue remodelling during embryonic development and it is known that osteoclasts exit the cell cycle during their differentiation This similarity incited us to investigate whether osteoclasts are senescent. Given the important role of oxygen, we assessed the influence of hypoxia on osteoclastogenesis and possible senescence status of these cells. Our results demonstrated that osteoclasts can indeed be considered senescent. Hypoxia (5% O2) delayed osteoclastogenesis, but did not affect their resorption capacity of bone.