The Role of Notum in Bone’s Response to Mechanical Loading and Aging

Osteoporosis is a silent, dangerous, pathology frequently undiagnosed until patients experience a major fracture. Fractures from osteoporosis lead to a 20% increase of mortality, revealing a need for novel anabolic therapies. Recently, mice lacking Notum protein expression were reported to have increased endocortical bone formation and strength. Notum is an inhibitory protein of the Wnt pathway, a major growth pathway in mammalians. The hypothesis for this work is Notum expression is affected by mechanical loading and aging. The goal of these studies is to investigate factors that could affect Notum expression, with the future direction of identifying factors that when pharmacologically modulated could promote anabolic bone growth. After establishing No-tum expression in the osteocyte cell line, MLOY4s, Notum expression was monitored in response to mechanical loading, mimicked via orbital shear stress for 15 min, 1hr, and 2hr. In addition, Notum expression was analyzed in aged bone. Our preliminary results suggest mechanical loading decreases Notum protein expression, while aging increases the expression of the Notum gene (p\u3c0.05). . With these results our hypothesis is supported, and future studies repressing Notum expression in bone as novel approach to promoting anabolic bone growth will be conducted