Office of Rare Diseases
Annual Report on the Rare Diseases and Conditions
Research Activities of the National Institutes of Health
National Institute of Dental Research (NIDR)
Overview of Rare Disease Research Activities Recent Scientific Advances in Rare Disease Research McCune-Albright Syndrome (MAS) McCune-Albright syndrome is characterized by precocious puberty, skin pigmentation and weak, deformed bones with marrow replaced by fibrous tissues and sharp needle-like bony deposits (fibrous dysplasia of bone). While mutations leading to the activation of a gene regulating signaling pathways in cells have been identified in patients, the mechanism leading to fibrous dysplasia in bone is not clear. NIDR scientists have shown that the expression of the gene in question is upregulated during maturation of precursor cells to normal bone-forming cells (osteoblasts), and that this pattern of expression is retained in fibrous dysplasia. Characterization of fibrous dysplastic tissues revealed that the fibrotic areas consist of an excess of cells that resemble pre-osteogenic cells, whereas the abnormal bone formed de novo within fibrotic areas represents the output of mature, but abnormal osteoblasts. The abnormal osteoblasts produce a bone matrix enriched in certain anti-adhesion molecules, and poor in certain pro-adhesive molecules found at high levels in normal bone formation. These data indicate that fibrous dysplasia of bone is a disease of cells in the osteogenic lineage, related to the upregulation of gene expression and its effects on bone cell function. They further suggest that a critical, physiological, maturation-related regulation of the gene involved in signaling pathways makes cells in the osteogenic lineage a natural target for the effects of mutations in the gene and may provide a clue as to why bone itself is affected in this painful, crippling disease. | |
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