| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2144681 | Matrix Biology | 2016 | 7 Pages |
•Fibrillin assemblies are low abundance structural components of skeletal tissues that regulate the bioavailability of locally produced TGFβ and BMP complexes.•Mutations in fibrillin-1 and fibrillin-2 cause severe skeletal abnormalities in patients afflicted with Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA), respectively.•Progressive bone loss in mouse models of MFS and CCA is associated with distinct defects in mesenchymal stem/progenitor cell differentiation that reflect the discrete contributions of fibrillin proteins to bone formation and metabolism.•Fibrillin assemblies therefore represent a unique experimental model to interrogate the dynamics of cells/matrix interactions that orchestrate the differentiation, homeostasis and repair of skeletal tissues.
The severe skeletal abnormalities associated with Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA) underscore the notion that fibrillin assemblies (microfibrils and elastic fibers) play a critical role in bone formation and function in spite of representing a low abundance component of skeletal matrices. Studies of MFS and CCA mice have correlated the skeletal phenotypes of these mutant animals with distinct pathophysiological mechanisms that reflect the contextual contribution of fibrillin-1 and -2 scaffolds to TGFβ and BMP signaling during bone patterning, growth and metabolism. Illustrative examples include the unique role of fibrillin-2 in regulating BMP-dependent limb patterning and the distinct impact of the two fibrillin proteins on the commitment and differentiation of marrow mesenchymal stem cells. Collectively, these findings have important implication for our understanding of the pathophysiological mechanisms that drive age- and injury-related processes of bone degeneration.
