Mechanical loading of the skeleton from daily activities determines to a large extent how the skeleton develops. Without proper exercise and loading activities, the skeleton will develop with insufficient strength, and osteoporotic fractures will eventually occur. Led by Alexander Robling, PhD this laboratory seeks to discover the molecular mechanisms by which bone tissue senses mechanical loading, by studying how several signal transduction pathways affect bone accumulation, and how cellular activity is altered by mechanical stimulation. This goal is addressed by investigating bone cell proliferation, differentiation and apoptosis, after mechanical loading in mice harboring various mutations in the Wnt/Akt/Bmp signaling pathways. The role of these pathways in mechanical disuse is also studied, using several in vivo models of disuse osteoporosis.