SGER: Altered Sensory Sensitivity in Osteocalcin Knockout Mice

Rutgers University New Brunswick, New Brunswick NJ

Investigators

Abstract

The skeleton is one of the defining characteristics of the Class Vertebrata. It provides structural support and a reservoir for calcium phosphate, but has been largely ignored as a contributor to overall body homeostasis. Osteocalcin (OC) is an abundant calcium binding protein component of bone matrix presumed to participate in control of mineralization. A relatively consistent percentage of OC is released to plasma (pOC) and generally reflects bone formation rate. Bones of mice depleted of osteocalcin by gene deletion (KO) are more densely mineralized than those of wild-type mice (WT). Interestingly, KO mice were also observed to differ in behavior and sensitivity to touch compared to WT mice. Because pOC concentration is also altered by external stimuli that can affect tactile sensitivity, its deletion may alter the availability of calcium required for nerve conduction. This project will confirm that KO mice that have no pOC are more sensitive to touch and to pain than WT. Mice will be evaluated by testing the following: (1) behavior in an open field environment, including those related to tactile sensitivity such as grooming and wall contact; (2) sensitivity to a heated surface and pressure on paws and other body areas exerted by calibrated Von Frey fibers; (3) re-evaluation of touch response and analysis of the stress hormone corticosterone following restraint and brief immersion in shallow room temperature water. These experiments will provide evidence that OC is necessary for normal tactile sensory function under both normal and stressful conditions. They will also provide evidence that bone functions as an endocrine organ with communication to the nervous system in the form of pOC.