Enhanced prostacyclin formation and Wnt signaling in sclerostin deficient osteocytes and bone.
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.
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Zachary C
ZC
Ryan
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Theodore A
TA
Craig
Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Jeffrey L
JL
Salisbury
Mayo Graduate School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Lomeli R
LR
Carpio
Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Meghan
M
McGee-Lawrence
Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Jennifer J
JJ
Westendorf
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: rkumar@mayo.edu.
Rajiv
R
Kumar
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006023:Glycoproteins / Q000172:deficiency*; D036341:Intercellular Signaling Peptides and Proteins; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D010011:Osteocytes / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; C486030:Sost protein, mouse; D051176:beta Catenin; D011464:Epoprostenol
Osteocytes; Prostacyclin; Sclerostin deficiency; Wnt