New studies implicate molecular clock genes, as well as pancreatic and enteric hormones, in bone homeostasis

Abstract

In the first study (1), entitled “The Molecular Clock Mediates Leptin-Regulated Bone Formation” and published in the September 9 issue of Cell, Gerard Karsenty and colleagues at Baylor College of Medicine in Houston, the Wellcome Trust Sanger Institute in Cambridge, U.K. and the Research Institute of Molecular Pathology in Vienna studied bone remodeling in mice genetically engineered to exhibit defects in Period (Per) or Cryptochrome (Cry), two key genetic components of the molecular clock involved in circadian regulation. “The idea is that bone remodeling is a homeostatic function, and since most homeostatic functions occur in a circadian manner, it makes sense that the molecular clock could play a role in bone remodeling,” Karsenty, Professor of Molecular and Human Genetics at Baylor, told BoneKEy-Osteovision. Karsenty and his colleagues found that mice lacking both Per1 and the Per2 PAS domain; or both Per1 and Per2; or both Cry1 and Cry2 all exhibited significant increases in bone mass in their vertebrae and distal femora. Furthermore, the investigators discovered that these mutants showed increases in osteoblast numbers and in mineral apposition and bone-formation rates.