Osteoimmunology: Exploring the Role of the Immune System in Regulating Bone in Health and Disease

Abstract

Our laboratory has pioneered the field of osteoimmunology. The laboratory is specialized in conducting in vivo studies in mice treated with PTH or subjected to ovariectomy. We use genetic models, retroviral transduction, bone marrow transplantation, T cell transfer and in vivo treatments with hormones, cytokines and antibodies. Typical end points include sophisticated flow cytometric analysis of bone marrow cells and microCT and histomorphometric analysis of bone structure. The lab is equipped with in vivo and in vitro microCT scanners. We have been the first to recognize that T cells play a pivotal role in the mechanism of action of estrogen and PTH in bone by regulating osteoclast and osteoblast development and function. We have shown that mice lacking T cells are protected against the bone loss induced by estrogen deficiency and hyperparathyroidism. We have has also shown that T cells regulate the number and function of mesenchymal stem cells. We are currently investigating the mechanism by which T cells mediate the expansion of hemopoietic stem cells caused by estrogen deficiency and PTH. Another main focus is to understand why “intermittent” PTH treatment causes bone anabolism while “continuous” PTH treatment causes bone loss. We hypothesize that the response to PTH depends on the effects of this hormone on T cell production of Wnt10b and TNF. A third project involves the use of intravital microscopy to study the effects of estrogen deficiency and PTH on the trafficking of T cells in the bone marrow.