Enhanced prostacyclin formation and Wnt signaling in sclerostin deficient osteocytes and bone

• Published in: Biochemical and biophysical research communications Vol. 448; no. 1; pp. 83 - 88
• Main Authors: Ryan, Zachary C., Craig, Theodore A., Salisbury, Jeffrey L., Carpio, Lomeli R., McGee-Lawrence, Meghan, Westendorf, Jennifer J., Kumar, Rajiv
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.05.2014
• Subjects: Animals; beta Catenin - metabolism; Bone and Bones - metabolism; Epoprostenol - biosynthesis; Glycoproteins - deficiency; Lymphoid Enhancer-Binding Factor 1 - biosynthesis; Mice; Mice, Knockout; Osteocytes; Osteocytes - metabolism; Prostacyclin; Sclerostin deficiency; Wnt; Wnt Signaling Pathway - drug effects; Wnt Signaling Pathway - genetics; Osteocytes; Prostacyclin; Sclerostin deficiency; Wnt
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.04.092

•Prostacyclin is increased in bone and osteocytes from sclerostin knockout mice.•Prostacyclin enhances differentiation and matrix mineralization of osteoblasts.•Increased osteocyte prostacyclin associates with increased β-catenin activity.•Blockade of Wnt signaling reduces prostacyclin production in osteocytes. We show that prostacyclin production is increased in bone and osteocytes from sclerostin (Sost) knockout mice which have greatly increased bone mass. The addition of prostacyclin or a prostacyclin analog to bone forming osteoblasts enhances differentiation and matrix mineralization of osteoblasts. The increase in prostacyclin synthesis is linked to increases in β-catenin concentrations and activity as shown by enhanced binding of lymphoid enhancer factor, Lef1, to promoter elements within the prostacyclin synthase promoter. Blockade of Wnt signaling reduces prostacyclin production in osteocytes. Increased prostacyclin production by osteocytes from sclerostin deficient mice could potentially contribute to the increased bone formation seen in this condition.