TGF-β Family Signaling in Connective Tissue and Skeletal Diseases
- 1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
- 2Department of Orthopedic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104
- 3Center for Research in FOP and Related Disorders, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104
- 4Howard Hughes Medical Institute, Bethesda, Maryland 21205
- 5Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104
- Correspondence: hdietz{at}jhmi.edu; shore{at}mail.med.upenn.edu
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↵6 These authors contributed equally to this work.
Abstract
The transforming growth factor β (TGF-β) family of signaling molecules, which includes TGF-βs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-β family members play different roles in these tissues, and their activities are often balanced with those of other TGF-β family members and by interactions with other signaling pathways. Perturbations in TGF-β family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-β family of signaling mediators and the extracellular matrix in connective tissues.
