Propeptide's normal role in healthy bone ID'd for the first time, shown to help bone development

Dr. Philip Trackman, professor of periodontology and oral biology at Boston University Henry M. Goldman School of Dental Medicine (GSDM), and his team identified for the first time the normal role of the lysyl oxidase propeptide (LOX-PP) in healthy bone formation. “We’re showing that LOX-PP naturally interferes with the effects of an important bone growth factor, effectively slowing the growth of pre-osteoblasts, cells that will ultimately make bone,” Dr. Trackman says.Because these cells cannot multiply and make bone at the same time, researchers think LOX-PP helps pre-osteoblasts enter the next phase of development, which is differentiation and production of bone. Think of this gene expression change as a “switch” from multiplication to bone making. “It’s counterintuitive in one sense but the process of bone formation is multi-step and complicated. So the control of each phase is important and that’s regulated by growth factors and apparently also by LOX-PP,” Dr. Trackman says.Dr. Trackman and colleagues are looking at other biochemical aspects of LOX-PP, too, specifically its role as a tumor suppressor. In July 2009, he showed how LOX-PP inhibits prostate cancer cell growth in vitro by inhibiting the activity of a key growth factor known as Fibroblast Growth Factor 2, or FGF-2. This was a key step in prostate cancer to bone metastasis research, as it was previously unknown how LOX-PP inhibits prostate cancer cell growth. Dr. Trackman’s team, including co-principal investigators Dr. Amitha Palamakumbura and Boston University School of Medicine (BUSM) Professor Dr. Gail Sonenshein, has shown that LOX-PP interferes with FGF-2 receptor binding and signaling with both prostate cancer cells and normal bone cells. Dr. Trackman continues to explore LOX-PP’s ability to inhibit breast cancer cell growth with Dr. Sonenshein.Dr. Trackman and his team were the first to show in 2004 that LOX-PP — not the LOX enzyme as previously believed — acts as a tumor suppressor. Contributors to the most recent paper include Dr. Siddharth Vora, PhD from GSDM, and the lab of Dr. Matthew Nugent in BU School of Medicine’s Department of Biochemistry. The paper, “Lysyl Oxidase Propeptide Inhibits FGF-2-induced Signaling and Proliferation of Osteoblasts,” appears in the March 5 Journal of Biological Chemistry and is available online at http://www.jbc.org/content/285/10/7384.full.