Beta-catenin mediates soft tissue contracture in clubfoot.
Journal Article (Journal Article)
The contracted tissues from clubfeet resemble tissues from other fibroproliferative disorders such as palmar fibromatosis. Beta-catenin-mediated signaling is a crucial pathway controlling the fibroproliferative response in many fibroproliferative disorders. To determine if beta-catenin signaling plays a role in clubfoot, contracted and less contracted tissues from clubfeet were studied using Western analysis to determine the protein level of beta-catenin. Primary cell cultures were established from these tissues, and they were treated with either lithium to increase beta-catenin or Dickkopf-1 to inhibit beta-catenin. RNA was extracted from the cells and analyzed to determine how beta-catenin regulates expression of Type III collagen, an extracellular matrix protein upregulated in contracted clubfoot tissue. There was a more than twofold increase in beta-catenin protein in the contracted tissues. Treatment with either lithium or Dickkopf-1 showed Type III collagen RNA expression positively correlated with the protein level of beta-catenin. These data support the concept that beta-catenin-mediated signaling plays an important role regulating contracture in clubfeet. Because pharmacologic agents are under development to block this signaling pathway, such drugs could be used in cases of severe stiffness to improve range of motion or to decrease the need for radical surgical approaches.
Full Text
Duke Authors
Cited Authors
- Poon, R; Li, C; Alman, BA
Published Date
- May 2009
Published In
Volume / Issue
- 467 / 5
Start / End Page
- 1180 - 1185
PubMed ID
- 19169765
Pubmed Central ID
- PMC2664424
Electronic International Standard Serial Number (EISSN)
- 1528-1132
Digital Object Identifier (DOI)
- 10.1007/s11999-008-0692-7
Language
- eng
Conference Location
- United States