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Enhanced prostacyclin formation and Wnt signaling in sclerostin deficient osteocytes and bone |
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| Authors: | Zachary C Ryan Theodore A Craig Jeffrey L Salisbury Lomeli R Carpio Meghan McGee-Lawrence Jennifer J Westendorf Rajiv Kumar |
| Institution: | 1. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA;2. Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA;3. Mayo Graduate School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA;4. Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA |
| Abstract: | 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. |
| Keywords: | Prostacyclin Osteocytes Sclerostin deficiency Wnt |
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