Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The LDL receptor-related protein 5 (LRP5) is a member of the LDL receptor family, which also includes the VLDL receptor and the apolipoprotein E receptor 2. The LRP5 is a co-receptor of Wnt located on the osteoblast membrane between two other receptors, Frizzled and Kremen. Frizzled and LRP5 bind to Wnt, thereby stabilizing beta-catenin and activating bone formation. When the dickkopf protein (Dkk) binds to Kremen and LRP5, this last undergoes internalization and therefore becomes unable to bind Wnt; this leads to degradation of beta-catenin and to inhibition of bone formation. In humans, loss of LRP5 function causes osteoporosis-pseudoglioma syndrome, which is characterized by congenital blindness and extremely severe childhood-onset osteoporosis (lumbar spine Z-score often < -4) with fractures. The G171V mutation prevents Dkk from binding to LRP5, thereby increasing LRP5 function; the result is high bone mass due to uncoupling of bone formation and resorption. The Z-scores in this condition can exceed +6 at the hip and spine. The LRP5 and Wnt/beta-catenin reflect the level of bone formation and play a central role in bone mass accrual and normal distribution. Furthermore, LRP5 may contribute to mediate mechanical loads within bone tissue. Identification of the Wnt/beta-catenin pathway is a breakthrough in the elucidation of pathophysiological mechanisms affecting bone tissue and suggests new treatment targets for patients with osteoporosis or specific malignant conditions such as myeloma and sclerotic bone metastases.
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PMID:LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. 1585 Sep 91

The Wnt-beta-catenin signaling pathway is involved in cell proliferation, differentiation and morphogenesis. Recently, mutations of the low-density lipoprotein receptor-related protein 5 (LRP5 ) gene, a receptor of this signaling, have been described to be associated with both osteoporosis-pseudoglioma syndrome and the high bone mass phenotype. It was found that the loss of function of the LRP5 in both human and mice yielded a decrease in bone formation, and an active mutation in this same gene resulted in a high bone mass trait. Moreover, several groups and we reported that single nucleotide polymorphisms in the LRP5 gene predicted the bone mass. This pathway also affects the pathogenesis of osteoarthritis and multiple myeloma. These findings indicate that Wnt-beta-catenin signaling pathway plays important roles in the skeletal biology.
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PMID:[Wnt-beta-catenin signaling in bone metabolism]. 1639 51