Mechanotransduction in Bone - Role of the Osteocyte Network

Abstract

The capacity of bone tissue to adapt to changing mechanical demands is well doculllcnted, but how the cells of bone perform this task remains poorly under stood. Over the last decade, significant progress has been made in understand ing how bone cells may sence and transduce mechanical signals cl rived from bone loading. These studies emphasize the role of osteocytes as the "profes ional" mechanosensory cells of bone, and the lacnno-canalicular network as the structure that mediates mechanosensing. The regulatory process of mechanical adaptation produces flow of interstitial fl uid in the bone lacunar-canalicular network along the smface of the osteocytes, which is likely the physiological signal for bone cell adaptive responses in vivo. As a result. the maintenance of a mechanically efficient architecture is likely to depend on a balance between the intensity and spatial distribution of the mechanical stimulus and the responsiveness of the bone cells. At the tissue level, strain distributions occur during lhe bone remodeling process, that show a relationship to the aclivity of osteoblasts and osteoclasis. T his suggests that the subsequent actival ion of osteoclasts and osteoblasts dur ing remodeling, is a strain-regulated phenomenon. I !ere, we present a theory that explnins the alignment of secondary osteons as \\'ell as the constancy of their di ameter as a product of osteoclast attraction and rejection by osteocytes under opposite local strains, leading to reduced and enhanced canalicular flow, respec til'ely. \"itric oxide is likely a key molecule in this process, ns its absence would lead to osteoclast attraction by causing osteocyte apoptosis, while its production by \\'Cll-strained osteocytes leads to osteoclast \\'ithdrawal.