Genetic selection for fast growth generates bone architecture characterised by enhanced periosteal expansion and limited consolidation of the cortices but a diminution in the early responses to mechanical loading

Abstract

Bone strength is, in part, dependent on a mechanical input that regulates the (re)modelling of skeletal elements to an appropriate size and architecture to resist fracture during habitual use. The rate of longitudinal bone growth in juveniles can also affect fracture incidence in adulthood, suggesting an influence of growth rate on later bone quality. We have compared the effects of fast and slow growth on bone strength and architecture in the tibiotarsi of embryonic and juvenile birds. The loading-related biochemical responses (intracellular G6PD activity and NO release) to mechanical load were also determined. Further, we have analysed the proliferation and differentiation characteristics of primary tibiotarsal osteoblasts from fast and slow-growing strains. We found that bones from chicks with divergent growth rates display equal resistance to applied loads, but weight-correction revealed that the bones from juvenile fast growth birds are weaker, with reduced stiffness and lower resistance to fracture. Primary osteoblasts from slow-growing juvenile birds proliferated more rapidly and had lower alkaline phosphatase activity. Bones from fast-growing embryonic chicks display rapid radial expansion and incomplete osteonal infilling but, importantly, lack mechanical responsiveness. These findings are further evidence that the ability to respond to mechanical inputs is crucial to adapt skeletal architecture to generate a functionally appropriate bone structure and that fast embryonic and juvenile growth rates may predispose bone to particular architectures with increased fragility in the adult.

Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression

“…While the significantly higher growth rate of the control animals during early puberty compared to late puberty reinforced other study results [51], there was no decrease in growth rates during late puberty in the GnRH-a group. The high growth rates associated with the GnRN-a group were consistent with increased growth rates following OVX in two month old animals [68]. One could argue that increased growth rates may result in a greater amount of non-lamellar bone forming on the periosteal surface which in turn decrease material properties of the bone and thus reduce bone strength [48,69].…”

“…Fast growing strains of chicks had weaker bones compared to slow growing strains replicating differences observed inmechanical strength results found between the GnRH-a and ER groups. The marrow cell proliferation rates were lower in the fast growing chick strains [68] and similar to the decrease in proliferation in the GnRH-a model with no significant changes in differentiation. The suppression of proliferation in the GnRH-a model may be due to the resulting estrogen suppression based on estrogen’s previously documented ability to directly modulate the differentiation of stromal cells into the osteoblast lineage [70].…”

“…Evidence of the effect of growth rates on mechanical strength comes from data using chicks as amodel [68]. Fast growing strains of chicks had weaker bones compared to slow growing strains replicating differences observed inmechanical strength results found between the GnRH-a and ER groups.…”

SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis

“…polyvinylalcohol (PVA; Grade GO4/140 Wacker Chemicals, Walton-on-Thames, UK) and chilled by precipitate immersion in n-hexane (BDH, Poole, UK; grade low in aromatic hydrocarbons) maintained at À708C and after removal stored at À708C. (38) After sectioning at 10 mm using the CryoJane tape transfer system (Instrumedics, Hackensack, NJ, USA) as previously described, (39,40) the distance between the chondro-osseous junction at the distal end of the growth plate and the fluorescing mineralization front was measured at 10 different points along the width of the section to obtain a daily BGR for each section. (39,41) Two sections per tibia were measured from 3 to 7 mice per phenotypic group.…”

Gene expression profiles of mandible reveal features of both calvarial and ulnar bones in the adult rat

“…6 The site-specific characteristics of bone cells is maintained in culture suggesting that the transcriptional machinery of the cell has retained the cellular 'identity' along with turnover characteristics. 7 In the mandible, bone tissue exhibits a complex pattern of behaviour with the alveolar bone being apparently more sensitive to the loss of mechanical stimuli (subsequent to tooth loss) than the basal bone. In this respect, the mandible could be considered to be a combination of attributes of both the cranial and axial skeleton in terms of its requirement for mechanical loading.…”