Discoveries

TSG-6 regulates the activity of bone resorbing cells

Mahoney, D.J., Swales, C., Athanasou, N.A., Bombardieri, M., Pitzalis, C., Kliskey, K., Sharif, M., Day, A.J., Milner, C.M. & Sabokbar, A. (2011). TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with OPG. Arthritis Rheum. 63, 1034-43. Wiley

In our previous work we have found that a protein called TSG-6, which is made during inflammation, is a novel regulator of bone turnover. For example, we discovered that this protein could regulate the activity of a type of bone cell (termed an osteoclast) that removes bone tissue in a process known as bone resorption. Here (with our collaborators at the University of Oxford) we have demonstrated that TSG-6 is made by osteoclasts themselves when they receive inflammatory signals and therefore can prevent these cells from resorbing bone. In other words, TSG-6 functions by an autocrine mechanism. Importantly, we also determined that TSG-6 works by preventing osteoclasts from anchoring firmly onto bone, which is necessary for them to be able to remove bone extracellular matrix (e.g. composed of type I collagen). TSG-6 does this by inhibiting the formation of intracellular structures in the osteoclast called F-actin rings (shown in red on Figure 1). In this study we also found that if you combine TSG-6 with another inhibitor of bone resorption (termed osteoprotegerin, or OPG for short) then both of these proteins have a much larger anti-resorptive effect than when they are given alone. This is called synergy and indicates that TSG-6 and OPG work through different mechanisms of action. Based on this and our previous studies we believe that TSG-6 has the potential to be developed as a novel therapeutic for conditions where there is excessive osteoclast-mediated bone breakdown, such as osteoporosis.

Tony Day & Caroline Milner