The importance of the Wnt/β-catenin pathway and LRP5 protein in bone metabolism of postmenopausal women

Abstract

Background. Postmenopausal osteoporosis is the most common metabolic bone disease among women. The Wnt signaling pathway has been known to be the critical regulator of osteoblastogenesis. Alterations in this mechanism may have consequences for bone remodeling in humans. Objectives. The aim of the study was to evaluate the frequency of genotypes and alleles of single nucleotide polymorphism (SNP) rs4988321 and rs312009 of LRP5 in Polish postmenopausal women with osteopenia (n = 109) and osteoporosis (n = 333). Potential correlations between genetic polymorphisms, bone mineral density (BMD), risk for bone fractures, and other clinical parameters were analyzed. Material and methods. Genomic DNA was extracted from the blood samples and the sequence polymorphisms of LRP5 gene were detected using real-time polymerase chain reaction (RT-PCR) methods with melting curve analysis. We also calculated the odds ratio (OR) for the LRP5 genotypes and the alleles. Then, we evaluated the effect of the LRP5 polymorphism on T-score, Z-score, L2L4AM, L2L4YA, L2L4BMD, body mass index (BMI), and other clinical parameters. Results. No statistically significant differences in the distribution of LRP5 rs312009 genotypes between the groups were observed. Furthermore, our findings indicate that there is no correlation between LRP5 genotypes and the clinical characteristics of women with osteopenia/osteoporosis. In contrast, there was an increased value of OR in heterozygotes for rs4988321, both in patients with osteopenia (OR = 1.47) and in those with osteoporosis (OR = 1.33). In our study, we were not able to calculate the OR parameter for the AA genotype due to its low prevalence in the population. Conclusions. Our results suggest that the Val667Met LRP5 (rs312009) polymorphism may contribute to an elevated risk for fractures in postmenopausal Polish women.

Associations of LRP5 Gene With Bone Mineral Density, Bone Turnover Markers, and Fractures in the Elderly With Osteoporosis

“…There is increasing evidence regarding the key role of the LRP5 gene in regulating bone metabolism (10,19). Here, we assessed the relationships of rs4988300 and rs634008 polymorphisms in the LRP5 gene with BTM, BMD values and fractures in a study population with SOP or osteoporotic fractures.…”

Disparity in bone mineral density of males and females with age

“…LRP5 and β catenin are found to significantly reduce in postmenopausal osteoporosis [18]. Increased reactive oxygen species (ROS) with aging process causes osteoblast apoptosis and also decrease osteoblastogenesis by inhibiting β catenin [19]. .…”

A new discovery of genetic polymorphisms of important genes in WNT pathway (LPR5 and AXIN1) associated with osteoporosis susceptibility in Chinese Han population

“…Therefore, more and more scholars are interested in the molecular mechanism between WNT signaling pathway related genes and osteoporosis. Up to now, many studies have been reported on the relationship between genetic polymorphism and susceptibility to osteoporosis (13)(14)(15)(16), but the mechanism of WNT signaling pathway in the development of osteoporosis is still unclear .…”