Spotlight on Research 2011

June 2011 (historical)

Blood Vessel Cells May Be Key to FOP Ossified Tissues, Say Scientists

Cells that line blood vessels are a main source of the excessive bone tissue that defines the rare inherited disease fibrodysplasia ossificans progressiva (FOP), say scientists at Harvard University and the University of Pennsylvania, who have published new research related to the disorder. Their work, supported, in part, by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), shows that these cells, called vascular endothelial cells, leave their blood vessel locations under conditions of inflammation and become stem-like cells that produce the problematic bone cells. The accumulation of extra bone gradually restricts movement in the bodies of people with FOP. The findings, reported in Nature Medicine, may result in new therapeutic targets to counter the disease.

In FOP, a mutated gene (ALK2) causes soft tissue to ossify, or to turn into cartilage or bone, after inflammation, and there is currently no way to reverse the damage. In collaboration with NIAMS grantee Frederick S. Kaplan, M.D., a longtime researcher of FOP, Bjorn R. Olsen, M.D., Ph.D., Dean for Research and Professor of Developmental Biology at the Harvard School of Dental Medicine, has spearheaded a team effort to examine the extra bone and cartilage in FOP patients and transgenic mice in hopes of unlocking the disorder’s secrets. The team found that the extra tissue contained molecular “markers” from vascular endothelial cells that were not present in normal bone and cartilage. Using cell culture techniques, the investigators were able to convert the endothelial cells to stem-like cells and then guide these cells into becoming bone cells. Through additional experimentation, the researchers were also able to confirm that the mutated (ALK2) gene that causes FOP was heavily involved in the endothelial cell to stem-like cell conversion.

For people with FOP and their families, the new research findings hold great promise. Today, treatment for the disease is mainly preventive, concentrating on early diagnosis and avoiding the kinds of injuries and inflammation that result in tissue ossification. But, what the scientists have learned about the disease’s pathology, and the factors responsible for it, will allow future therapies to be directed to these factors. And, the scientists’ discovery of the mechanism of endothelial to stem-like to bone cell conversion should have broader applications in the fields of tissue engineering and regenerative medicine.

“The secrets of FOP have long remained hidden from researchers,” says Dr. Olsen. “But we think we’ve taken some important steps toward understanding and eventually treating the disease.”

In addition to the NIAMS, supporters of the study included the National Cancer Institute, a component of the NIH, and the International Fibrodysplasia Ossificans Progressiva Association.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

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Medici D, Shore EM, Lounev VY, Kaplan FS, Kalluri R, Olsen BR. Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med. 2010 Dec; 16(12):1400-6. Epub 2010 Nov 21. PubMed PMID: 21102460.