Combined Effects of Mechanical Loading and Piezo1 Chemical Activation on 22-Months-Old Female Mouse Bone Adaptation

Abstract

With age, bones mechanosensitivity is reduced, which limits their ability to adapt to loading. The exact mechanism leading to this loss of mechanosensitvity is still unclear, making developing effective treatment challenging. Current treatments mostly focus on preventing bone mass loss (such as bisphosphonates) or promoting bone formation (such as Sclerostin inhibitors) to limit the decline of bones mass. However, treatments do not target the cause of bone mass loss which may be, in part, due to the bone's inability to initiate a normal bone mechanoadaptation response. In this work, we investigated the effects of 2 weeks of tibia loading, and Piezo1 agonist injection in vivo on 22-month-old mouse bone adaptation response. We used an optimized loading profile, which induced high fluid flow velocity and low strain magnitude in adult mouse tibia. We found that tibia loading and Yoda2 injection have an additive effect on increasing cortical bone parameters in 22-month-old mice. In vivo osteocytes calcium signaling imaging suggests that Yoda2 is able to reach osteocytes and activate Piezo1. This combination of mechanical and chemical stimulation could be a promising treatment strategy to help promote bone formation in patients who have low bone mass due to aging.

Keywords: Piezo1; aging; bone; in vivo calcium signaling; mechanoadaptation; osteocytes; tibia loading.