Denhardts graduate student Kathryn Wang, a co-author on the PNAS paper, had previously conducted experiments in which the mouse was positioned in such a way as to produce hind limb unloading. This simulated weightless condition produced OPN-dependent bone loss in the hind limbs and provided a potential testing ground for possible OPN antibodies. The specialized equipment for that experiment was supplied by another co-author on the paper, Yufang Shi, a professor in the Department of Molecular Genetics, Microbiology and Immunology at Robert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New Jersey.
Shi, an authority on stress, suggested that along with the bone loss studies, the Rutgers researchers should look at the spleen and thymus the organs responsible for most of the animals immune cells. If stress affects the spleen and thymus so that they atrophy, the immune system becomes impaired. People under severe stress often get sick.
The Rutgers scientists took their colleagues advice and compared the OPN-deficient knock-out mice to normal mice, with some dramatic results.
To our astonishment and surprise, the OPN-deficient animals responded differently to the stress than the normal controls, Denhardt said. We had no basis to expect this, but the spleen and thymus of the OPN-deficient animals remained normal whereas there was atrophy of the spleen and thymus in the normal controls. This was a novel and totally unexpected result for which we have no explanation at this time. The next phase of our research will ask what exactly is going on.
The stressed normal mice also displayed elevated levels of corticosterone a hormone known to induce apoptosis (programmed cell death), a process evident in the spleen and thymus of these mice and a possible mechanism underlying the atrophy.
Denhardt said that t
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Rutgers, the State University of New Jersey