My research concerns regulation of skeletal calcium homeostasis at the cellular and molecular level.  Current studies address the signal transduction pathways involved in cell-mediated effects of acidosis on bone compared with calcemic hormones such as parathyroid hormone.  Model systems used are neonatal mouse calvariae in organ culture as well as primary bone cells and osteoblastic osteosarcoma cell lines.  In our in vitro model of metabolic acidosis, the cell-mediated effects of protons on bone appear to be very similar to calcemic hormone effects on bone. The effect of acidosis is mediated by prostaglandin E2 production in the osteoblast via activation of cyclooxygenase 2 and may be activated by interaction with a specific proton receptor. We are beginning to characterize responses in two proton receptor knockout mouse models, as well as defining a Ca-dependent initial signaling step in the osteoblast and its role in proton-mediated changes in osteoblast activity. 

I also collaborate on projects related to understanding the molecular basis for the genetic defect in the regulation of vitamin D receptors in a strain of hypercalciuric, stone-forming rats.

Krieger, N.S., Parker, W.R., Alexander, K.M. and Bushinsky, D.A. Prostaglandins regulate acid-induced cell-mediated bone resorption.  Amer. J. Physiol. 279:F1077-1082, 2000.

Krieger, N.S., Frick, K.K., and Bushinsky, D.A. Effect of cortisol on acid-induced bone    resorption in vitro. J. Amer. Soc. Nephrology 13:2534-2539, 2002.

Krieger, N.S., Frick, K.K. and Bushinsky, D.A. Mechanisms of acid effects on bone.  Curr. Opin. Nephr. Hypertens. 13: 423-436, 2004.

Krieger, N.S., Frick, K.K., LaPlante, K. and Bushinsky, D.A.  Regulation of COX-2 mediates acid-induced bone calcium efflux in vitro.  J. Bone Min. Res. 22: 907-918, 2007.