SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development

Abstract

Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity is essential for normal cardiovascular development, and altered activity of these growth factors causes maldevelopment of the cardiac outflow tract and great arteries. In the present study, we show that SOST, a Dan family member reported to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of the great arteries containing smooth muscle cells. The ascending aorta, aortic arch, brachiocephalic artery, common carotids, and pulmonary trunk were all associated with SOST expressing smooth muscle cells, while the heart itself, including the valves, and more distal arteries, that is, pulmonary arteries, subclavian arteries, and descending aorta, were negative. SOST was expressed from embryonic day 15.5 up to the neonatal period. SOST expression, however, did not correspond with inhibition of Smad-dependent BMP activity or ␤-catenin-dependent Wnt activity in the great arteries. Activity of both signaling pathways was already down-regulated before induction of SOST expression. Developmental Dynamics 236:606 -612, 2007.

Sclerostin and Dickkopf-1 as Therapeutic Targets in Bone Diseases

“…Figure 2 highlights the osteocytic expression of sclerostin in mouse, rat, monkey, and human bone. Extraosseous sclerostin expression has been described in specific regions of the developing embryonic and neonatal heart, although sclerostin expression was not detected in adult cardiac tissue (88,89). Most recently, Zhu et al (90) showed that sclerostin expression increases with calcification of vascular smooth muscle cells and expression of sclerostin in calcified aortas from the Enpp1 KO mice.…”

Sclerostin expression and functions beyond the osteocyte

“…Sclerostin has widely been viewed as an osteocyte-specific protein, despite early studies noting SOST RNA in multiple human and mouse tissues, including cartilage, kidney, heart, and liver (1, 2, 15). More recently, using Sost promoter LacZ reporter mice, Collette, et al, further expanded this list, documenting Sost LacZ reporter expression in the epididymis and vas deferens of the testis, the pyloric sphincter, the carotid arteries, and parts of the cerebellum (16).…”

Quantitative in situ fluorescence imaging to unveil the morphological and functional heterogeneity of osteocytes

“…Sclerostin is a hallmark protein of osteocytes, which negatively regulates proliferation and differentiation of osteoblast, thus regulating bone formation [4][5][6][7][8]. Mechanical loading negatively regulates the expression of sclerostin and therefore, this molecule bridges mechanical loading to bone and bone metabolism [9][10][11].…”