The Relationship Between LRP-5 and LRP-6 Gene Mutations and Postmenopausal Type 2 Diabetes and ObesityLi, Li, Lu
et alClin Med Insights Endocrinol Diabetes (2025) 18, 11795514241307180
Abstract: Single nucleotide polymorphisms (SNPs) in the low-density lipoprotein receptor-related protein 5 (LRP5) and the low-density lipoprotein receptor-related protein 5 (LRP6) genes have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity (OB). This study aimed to evaluate the polymorphisms in LRP5 and LRP6 genes in postmenopausal patients with T2DM and OB.Participants were categorized into the Non-T2DM group (n = 53) and the T2DM group (n = 89) based on glycemic levels. Baseline data and biochemical indices were collected, Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry, and SNPs at the LRP5 and LRP6 loci were assessed by time-of-flight mass spectrometry.1. There was a statistical difference in the distribution of genotypes (CC/CT) at locus rs4988331 (χ2 = 67.940, P = .000) and in the distribution of alleles (C/T) between the T2DM and non-T2DM groups (χ2 = 50.506, P = .000). Additionally, there were significant differences in the allele (G/A) at locus rs11054704, and both allele (G/T) and genotype (GG/GT) distributions at locus rs1181334 between the OB group and the normal weight group (P < .05). 2. OB was identified as a risk factor for T2DM in individuals with the wild-type at locus rs1181334, and the interaction between wild-type and mutant was significant (P < .05). 3. Multifactorial logistic regression analysis revealed that BMD (OR 3.755; 95% CI, 1.215-11.608) and triglyceride-glucose (TyG) index (OR 2.855; 95% CI, 1.361-5.986) were risk factors for T2DM in postmenopausal women, whereas alkaline phosphatase (ALP; OR 0.970; 95% CI, 0.945-0.995) and rs4988331 mutation (OR 0.018; 95% CI, 0.006-0.060) were protective factors.Mutations at the LRP5-rs4988331 locus, as well as the LRP6-rs11054704 and rs1181334 loci, may be associated with the development of T2DM and OB in postmenopausal women.© The Author(s) 2025.
Incident Vertebral Fractures During Romosozumab Treatment in a Patient With a Pathogenic LRP5 Variantvan Velsen, Wijnen, Muradin
et alJCEM Case Rep (2025) 3 (1), luae238
Abstract: A defect in the canonical Wnt-β-catenin pathway may lead to reduced bone strength and increased fracture risk. Sclerostin is a key inhibitor of this pathway by binding to low-density lipoprotein (LDL) receptor-related protein (LRP)-5/6, thereby reducing bone formation. The effectiveness of romosozumab, a human monoclonal antibody that binds sclerostin and prevents this inhibitory effect, has been questioned in patients with inactivating genetic variants in LRP5 or LRP6. We present a 67-year-old woman with severe osteoporosis with 4 grade 2 vertebral fractures due to a heterozygous pathogenic variant in LRP5. She was treated with romosozumab for 1 year, after which a routine follow-up spine x-ray revealed 5 new vertebral fractures, despite a strong increase in bone mineral density (BMD) (lumbar spine [LS] + 58%; femur neck [FN] + 23%), although overestimated at LS because of the vertebral fractures. This suggests that in patients with loss-of-function LRP5 variants, romosozumab is able to increase BMD. However, it is unclear whether the progressive vertebral fractures are due to the severe osteoporosis in relation to the start of romosozumab or a diminished responsiveness related to her LRP5 variant. Further evaluation is needed on the effect of romosozumab on BMD and fracture outcomes in patients with a likely defective LRP5/6 receptor.© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.
Effect of bioactive compounds of Mucuna pruriens on proteins of Wnt/β catenin pathway in pulmonary hypertension by in silico approachBhosle, Bagali, Parvatikar
et alIn Silico Pharmacol (2024) 12 (2), 110
Abstract: Modulation of the Wnt/β-catenin signaling pathway may aid in discovering new medications for the effective management of pulmonary artery hypertension (PAH). Given the therapeutic potential of Mucuna pruriens in several diseases, the present study aimed to analyze interactions of different bioactive compounds of Mucuna pruriens plant seeds with Wnt/β-catenin pathway targeting its various components like Wnt 3a, Frizzled 1, LRP 5/6, β-catenin, Disheveled, cyclin D1 by in silico analysis. The proposed work is based on computational analysis including ADME/T properties, by a Swiss ADME server. To understand the molecular interaction pattern Schrodinger, suit a stand-alone software was used to predict the interaction of bioactive molecules of Mucuna Pruriens with target proteins that are involved in Wnt/ β catenin pathway. Further, the simulation pattern of the top docked complex was subjected to MD simulation in Desmond for 100 ns. Bioactive molecules from Mucuna Pruriens have drug-like properties and minimal toxicity. Further, the docking study revealed that among the nine compounds, three compounds (Gallic acid, L-dopa, and β-sitosterol) showed good interaction with target proteins. As gallic acid showed good interaction with all target proteins, the docked complex was subjected to MD simulation which was stable throughout the simulation time in terms of RMSD and RMSF. These findings suggest that the bioactive molecules of Mucuna pruriens compounds have potential therapeutic value in the treatment of pulmonary vascular disease. Further, in vivo and in vitro studies are necessary to determine its efficacy and validate its pharmacological activity conclusively.© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Protective effects of electroacupuncture on senile osteoporosis in ratsZhou, Wang, Qu
et alAcupunct Med (2024) 42 (6), 334-341
Abstract: The objectives were to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in aged rats and investigate the underlying mechanisms.This study included aged (24-month-old; n = 16) and young (3-month-old; n = 8) male Sprague-Dawley rats. Aged rats were further randomized 1:1 to an aged control group (Aged; n = 8) and an EA treatment group (EA; n = 8). The 3-month-old rats served as young controls (Young). EA rats received EA at ST36, SP6, GB34 and SP10 bilaterally for 30 min a day, 5 days a week, for 8 weeks.EA significantly increased serum markers of bone formation in Aged rats. There were no significant differences in serum markers of bone resorption between EA and Aged rats. Deterioration of bone mineral density (BMD) and trabecular bone architecture was observed in the Aged group, while EA significantly increased BMD of the left femur and L5 vertebral body in aged rats. Aging-induced deterioration of trabecular bone architecture was partially reversed in EA rats. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells in EA compared with Aged groups. The mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells in EA compared with Aged groups.EA may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. EA may represent a therapeutic option for senile osteoporosis.
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