Spatial Correlation of Trabecular Bone Tissue Strain Invariants and Sclerostin Expression

Quantifying the spatial relationship between mechanical deformation and signaling protein expression within trabecular bone is essential to understanding the mechanobiological signaling cascade that maintains bone health. Interventions such as pharmaceuticals that can leverage the mechanobiological signaling processes in trabecular bone can provide new therapeutic approaches for bone repair for bone diseases, such as osteoporosis. There were 2 million cases of osteoporotic fracture in 2005, with a treatment cost of $16.9 billion, and are expected to increase to more than 3 million fractures at a cost of $25 billion by 2025. Bone is primarily a load-bearing organ and is well known to be mechanoresponsive. As osteocyte mechanobiology is believed to be governed by fluid flow in bone canaliculi, volume changing and volume preserving deformations may play distinct roles in mechanobiology. Thus, improved understanding of the mechanics can inform treatment strategies and fracture prevention. Finite element models of porcine vertebral trabecular bone explants were used to calculate the spatial strain field. Two-point correlation was used to quantify the spatial relationship between dilatational (volume changing) and deviatoric (volume preserving) strain within the bone matrix. The results consistently showed a strong spatial relationship between high deviatoric strain and negative dilatational strain when the bone samples were subjected to compression.

Immunohistochemistry was coupled with bioreactor culture and computational modeling to link local mechanical behavior to biological response. Trabecular bone explants from female pigs were cultured in a bioreactor and subjected to controlled loading. Sclerostin protein expression – a key molecule regulating osteoblast differentiation - was compared between loaded and unloaded samples. A greater percentage of osteocytes expressed sclerostin in the unloaded bones. Osteocytes that did not express sclerostin in loaded bones were preferentially found near locations of high deviatoric strain. Since the high deviatoric strain locations are likely coincident with high dilatational strain in this loading condition, it may not be possible to segregate the specific underlying mechanical signal. However, the results demonstrate that mechanical down regulates sclerostin expression, and that the effect is localized to high deformation regions within the trabecular structure.