A ground-based, experimental model used to simulate astronaut weightlessness in space has provided Rutgers scientists an opportunity to study the effects of stress on immune organs.
Earlier collaborative research with Japanese scientists employing this model implicated the protein osteopontin (OPN) in bone mineral loss associated with simulated weightlessness in mice. This research was made possible by the creation at Rutgers of a mouse unable to make OPN (a “knock-out” mouse). Studies with this Rutgers mouse have demonstrated that OPN likely plays a role in a variety of human problems including cancer metastasis, multiple sclerosis and other autoimmune diseases, osteoporosis and certain inflammatory responses.
The new study, which also simulated weightlessness, demonstrated that OPN is required for the atrophy of immune organs brought on by the stress resulting from hindlimb unloading – a technique employed to simulate weightless conditions by lifting the animal's body weight off its hind legs. Results are presented Sept. 3 online in the Proceedings of the National Academy of Sciences (PNAS) and in the Sept. 11 print issue.
“The bone loss seen in astronauts or bedridden patients is not a stress issue,” explained David Denhardt, a professor in the Department of Cell Biology and Neuroscience at Rutgers, The State University of New Jersey. “They are experiencing a loss of weight bearing on the bones, and the loss of bone mineral is a direct result of this load reduction.”
The presence of OPN, a feature common to both the bone loss and the organ atrophy, is produced by two different causes – weightlessness and stress – coincidentally related to the same laboratory conditions.
OPN is the continuing focus of Denhardt's research interests. His long-term goal is to develop an OPN antibody – a monoclonal or target-specific antibody – that will inhibit OPN function in lab mice, and ultimately, in humans. This antibody could prove useful in treating the many destructive diseases associated with OPN.
Denhardt's 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 School–University of Medicine and Dentistry of New Jersey.