Millions of Americans suffer from bone loss, primarily from osteoporosis, rheumatoid arthritis, and chronic kidney disease.¹ Nearly all of the current bone treatments do not improve the bone conditions but rather prevent bone loss, failing to eliminate the possibility of future complications. As a result, the effects of bone loss disorders on the economy are staggering: according to Blume and Curtis, the cost of osteoporosis and fractures in 2002 was estimated to be $16 billion.² Indexed to 2008, the national cost of osteoporosis and fractures was $22 billion; the cost is likely higher in 2015. Thus, discovering better treatments for osteoporosis and bone disorders may alleviate these extraordinary healthcare costs by preventing fractures in the first place.

In order to provide anabolic therapies, more research in bone metabolism is needed. Recent discoveries have demonstrated that WNT signaling, specifically the canonical pathway, may play a key role in bone homeostasis.^3,4 A study published this year suggests that this pathway might be useful for targeting anabolic action in bone.⁵

Disruption of PTEN, an intracellular phosphatase that indirectly inhibits the activity of AKT by reversing the phosphorylation of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol (3,4,5)-trisphosphate, results in high bone mass.⁶ AKT activates downstream signaling nodes in the WNT pathway, particularly β-catenin. When AKT activity is not disturbed by PTEN, it is able to interact with a multitude of other pathways, especially those involved in cell growth and survival. However, it is unclear if the bone-building activity of enhanced AKT activation requires β-catenin. We seek to clarify this ambiguity by disrupting both PTEN and β-catenin in bone cells and observing the resulting bone structure and mineral composition. If disrupting both PTEN and β-catenin results in bones with lower mineral densities, this would suggest that the bone-related activity of AKT depends on β-catenin. However, if this is not the case, then there may be an alternative pathway through which AKT triggers high bone mass.