Bony Immunology: 1st Annual International Conference on Osteoimmunology Crete, Greece, May 28–June 2, 2006

Bone marrow cavities fill up with fat in mice lacking the transcription factor EBF-1 (early B cell factor-1), according to data The evolutionarily conserved EBF transcription factors (EBF-1–4) are required for the development of olfactory neurons and B cells. EBF-1 also promotes fat cell (adipocyte) differentiation when overexpressed in preadipocyte cell lines, but the mecha-nism—and in vivo significance—of this finding was unclear. To investigate the role of EBF-1 in fat formation, Horowitz and colleagues examined mice lacking the transcription factor. In addition to having no B cells, the mice had fat in all the wrong places. Subcutaneous fat was almost entirely missing, possibly explaining their previously described wasted appearance. The mice instead had fat where their bone marrow should be. Excess fat wasn't their only problem. The EBF-1–deficient mice also had increased bone mass due to an overabundance of osteoblasts. The combined fat–bone phenotype prompted Horowitz to suggest that EBF-1 might regulate gene expression in a common adipocyte–osteoblast precursor cell, as these cells are known to arise from a common progenitor. But this hunch is difficult to test. Unlike in B cell development , few markers have been identified to distinguish osteoblast precursor cells at various stages of differentiation. In this respect, says Horowitz, " bone biologists are 15 years behind immunologists. " The only targets of EBF-1 identified thus far are those involved in B cell development. One of those targets, the B cell– specific transcription factor encoded by Pax5, is also required for bone maintenance. But in bone, the relationship between EBF-1 and Pax5 is more complicated, as the absence of Pax5 causes severe bone loss—the opposite of the defect caused by EBF-1 deficiency. Low estrogen—during menopause in women or induced by ovary removal in rodents—causes osteoporosis. has put the blame for this bone loss squarely on T cells and, at the meeting, he provided corroborating evidence. But new data from Reinhold Erben (University of Veterinary Medicine, Vienna, Austria) seems to exonerate these cells. Perhaps the strongest evidence that T cells cause bone loss when estrogen is in short supply comes from T cell–deficient (" nude ") mice. In past studies, Pacifici and colleagues showed that nude mice—unlike wild-type mice—do not develop osteoporosis when their ovaries are removed. Bone loss kicks in when T cells are transferred into the mice. This effect depends on T cell production of the cytokine TNF, which causes stromal cells to produce growth …