Abstract: FR-PO509
Sclerostin, a Potential Mediator in the Bone-Vascular Axis
Session Information
- Bone and Mineral Metabolism: Basic
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- De maré, Annelies, University of Antwerp, Wilrijk, Belgium
- Opdebeeck, Britt, University Antwerp, Wilrijk, Belgium
- Neven, Ellen, University of Antwerp, Wilrijk, Belgium
- D'Haese, Patrick C., University Antwerp, Wilrijk, Belgium
- Verhulst, Anja, University of Antwerp, Wilrijk, Belgium
Background
The Wnt/β-catenin signaling, one of the most important bone anabolic pathways, might also be a major player in the crosstalk within the bone-vascular-axis. When pathologically disturbed, this axis results in the concomitant occurrence of disturbed bone metabolism and vascular calcification (VC). A hallmark of these VCs is the transdifferentiation of vascular smooth muscle cells (VSMCs) towards bone-forming (osteochondrogenic) cells. In the current study we investigated parameters related to the Wnt/β-catenin signaling cascade and its inhibitor sclerostin.
Methods
Rats were given 0.3mg warfarin/g diet to induce VC. Rats not receiving warfarin were included as controls. Rats were sacrificed at different time-points, i.e. after 4, 6, 8 and 10 weeks of warfarin treatment, to follow up the development of VC. At sacrifice; VC, aortic mRNA expression and immunohistochemistry, bone status and serum biochemistry were analyzed.
Results
Results showed a time-dependent increase in VC in warfarin-treated rats. Aortic calcium concentration significantly differed from controls in 4-wk treated rats (p=0.0286), reaching a 50-fold increase in 10-wk treated rats (p=0.0061). Furthermore, aortic mRNA levels of osteochondrogenic transdifferentiation markers (Sox9, p=0.0317 and Cbfa1, p=0.0635) and β -catenin (regulating target gene transcription, p=0.0159) were upregulated. Interestingly, this went along with an upregulation of aortic mRNA expression (p=0.0159) and protein levels of sclerostin, as well as serum levels of this protein which became significant (p=0.0381) in 10-wk treated rats compared to controls. Finally, a mild but significant (p= 0.0095) decrease in bone formation parameters was observed in 10-wk treated warfarin rats.
Conclusion
Our results support the hypothesis that VSMCs transdifferentiate towards osteochondrogenic cells and thereby also express genes/proteins associated with the Wnt/β-catenin signaling, including its inhibitor sclerostin. The latter thereby may act as a negative feedback protein to prevent excessive (vascular) calcifications, similar to its function in bone. Sclerostin might also spillover from the vessels to the circulation (high serum sclerostin levels) causing mild inhibition of bone formation.
Funding
- Government Support - Non-U.S.