Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway
Yewei Liu, Adam Lehar, Renata Rydzik, Harshpreet Chandok, Yun‐Sil Lee, Daniel W. Youngstrom, Joshy George, Martin M. Matzuk, Emily L. Germain‐Lee, Se‐Jin Lee
Abstract
loss are mostly restricted to the posterior region, implying that locally produced FST plays a much more important role than circulating FST with respect to regulation of muscle and bone. Finally, we show that targeting receptors for these ligands specifically in osteoblasts leads to dramatic increases in bone mass, with trabecular bone volume fraction being increased by 12- to 13-fold and bone mineral density being increased by 8- to 9-fold in humeri, femurs, and lumbar vertebrae. These findings demonstrate that bone, like muscle, has an enormous inherent capacity for growth that is normally kept in check by this signaling system and suggest that the extent to which this regulatory mechanism may be used throughout the body to regulate tissue mass may be more significant than previously appreciated.