Intraperitoneal injection of LMW-OPS significantly suppressed tumor growth in syngeneic tumor models using CMT93 and CT26 sphere cells, whereas it had no inhibitory effect on the proliferation of either cell line.
The authors report a case of familial exudative vitreoretinopathy in the spectrum of osteoporosis pseudoglioma syndrome associated with novel mutations of the LRP5 and TSPAN12 genes that resulted in a phenotype similar to bilateral persistent fetal vasculature.
Using LRP5-related proteins, such as the low-density lipoprotein receptor (LDLR) and nidogen as reference models, a homology model of LRP5 suggested that the observed mutations may affect the molecular interactions of LRP5 and so lead to the observed OPPG phenotypes.
Our data suggest an important component of the skeletal fragility phenotype in individuals affected with osteoporosis-pseudoglioma is inadequate processing of signals derived from mechanical stimulation and that PTH might be an effective treatment for improving bone mass in these patients.
The TCIRG1 gene was shown to underly autosomal recessive osteopetrosis (ARO), and, recently, mutations in the LRP5 gene were found both in the osteoporosis-pseudoglioma syndrome and the high bone mass trait.
Loss of function of Sost or treatment with a Sclerostin neutralizing antibody improves bone properties in animal models of Osteoporosis Pseudoglioma syndrome (OPPG), likely due to action through the LRP6 receptor, which suggests patients may benefit from these therapies.
Here, we report two novel mutations in the INPPL1 gene and show that cell migration is very much decreased in fibroblasts derived from three OPS patients as compared with control individuals.
Loss of function of Sost or treatment with a Sclerostin neutralizing antibody improves bone properties in animal models of Osteoporosis Pseudoglioma syndrome (OPPG), likely due to action through the LRP6 receptor, which suggests patients may benefit from these therapies.
Furthermore, we discuss provocative reports suggesting novel approaches through inhibitors of this pathway to treat rarer diseases such as Osteoporosis-Pseudoglioma Syndrome (OPPG), Osteogenesis Imperfecta (OI), and Sclerosteosis/Van Buchem disease.
Our finding of INPPL1 mutations in OPS, a severe spondylodysplastic dysplasia with major growth plate disorganization, supports a key and specific role of this enzyme in endochondral ossification.
Mutation of human LRP5 is responsible for osteoporosis-pseudoglioma syndrome and disruption of Lrp6 in mice causes similar effects to mutation of several different Wnt genes.
The Wnt pathway was found to be involved in bone biology in 2001-2002 with the discovery of a (G171V) mutation in the lipoprotein receptor-related protein 5 (LRP5) that resulted in high bone mass and another mutation that completely inactivated Lrp5 function and resulted in osteoporosis pseudoglioma syndrome (OPPG).
Osteoporosis pseudoglioma syndrome (OPPGS) is a rare autosomal recessive genetic disorder characterised by congenital blindness and osteoporosis, caused by biallelic mutations in the LRP5 gene.
The authors report a case of familial exudative vitreoretinopathy in the spectrum of osteoporosis pseudoglioma syndrome associated with novel mutations of the LRP5 and TSPAN12 genes that resulted in a phenotype similar to bilateral persistent fetal vasculature.
Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive condition of congenital blindness and severe childhood osteoporosis with skeletal fragility, caused by loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene.
To assess whether loss of sclerostin is anabolic in OPPG, we measured bone properties in a mouse model of OPPG (Lrp5(-/-)), a mouse model of sclerosteosis (Sost(-/-)), and in mice with both genes knocked out (Lrp5(-/-);Sost(-/-)).
Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signaling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading.