Bone Overgrowth-associated Mutations in Lrp4 Impair Sclerostin- Facilitator Function
نویسندگان
چکیده
Olivier Leupin 1* , Elke Piters 2* , Christine Halleux 1 , Shouih Hu 1 , Ina Kramer 1 , Frederic Morvan 1 , Tewis Bouwmeester 3,4 , Markus Schirle 5 , Manuel Bueno-Lozano 6 , Feliciano J Ramos Fuentes 6 , Peter H Itin 7 , Eveline Boudin 2 , Fenna de Freitas 2 , Karen Jennes 2 , Barbara Brannetti 8 , Nadine Charara 9 , Hilmar Ebersbach 9 , Sabine Geisse 9 , Chris X. Lu 10 , Andreas Bauer 3,4 , Wim Van Hul 2 and Michaela Kneissel 1
منابع مشابه
Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption.
Bone mass is maintained by balanced activity of osteoblasts and osteoclasts. Lrp4 (low-density lipoprotein receptor related protein 4) is a member of the LDL receptor family, whose mutations have been identified in patients with high-bone-mass disorders, such as sclerosteosis and van Buchem diseases. However, it remains unknown whether and how Lrp4 regulates bone-mass homeostasis in vivo. Here ...
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Lrp4 is a multifunctional member of the low density lipoprotein-receptor gene family and a modulator of extracellular cell signaling pathways in development. For example, Lrp4 binds Wise, a secreted Wnt modulator and BMP antagonist. Lrp4 shares structural elements within the extracellular ligand binding domain with Lrp5 and Lrp6, two established Wnt co-receptors with important roles in osteogen...
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Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, exp...
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SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a h...
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Osteoporosis pseudoglioma syndrome (OPPG) is a rare genetic disease that produces debilitating effects in the skeleton. OPPG is caused by mutations in LRP5, a WNT co-receptor that mediates osteoblast activity. WNT signaling through LRP5, and also through the closely related receptor LRP6, is inhibited by the protein sclerostin (SOST). It is unclear whether OPPG patients might benefit from the a...
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