Risk Genetic Variants (IL-10) for Osteoporosis in Han Population from Northwest China.

Background: Osteoporosis (OP) is a common metabolic bone disease characterized by loss of bone mass. IL-10 is considered to be a powerful immune and inflammatory suppressor. This study aimed to assess association between genetic loci in IL-10 and susceptibility to OP. Methods: Association analysis between IL-10 genetic loci and OP risk through SNPStats online software. FPRP analysis (false-positive report probability) verified whether the positive results were noteworthy findings. Linkage disequilibrium (LD) and haplotype analysis were completed by Haploview 4.2 and SNPStats. Multi-factor dimensionality reduction (MDR) was used to assess interaction of SNP-SNP in susceptibility to OP. Results: Allele "G" of IL-10-rs1554286 (OR = 1.21, p = 0.013), allele "C" of IL-10-rs1518111 (OR = 1.22, p = 0.011), allele "C" of IL-10-rs3024490 (OR = 1.20, p = 0.018), and allele "G" of IL-10-rs1800871 (OR = 1.21, p = 0.015) were risk factors for OP. In females, smoking, drinking, or aging ≤60 years old participants, the above genetic loci are also significantly associated with the increased risk of OP. FPRP analysis showed that all positive results are noteworthy findings. There are significant differences in serum levels of uric acid, mean hemoglobin concentration, or mean hemoglobin among different genotypes of IL-10 gene loci. MDR showed that four loci model composed rs1554286, rs1518111, rs3021094, and rs1800871 is the best model for predicting OP risk. Conclusion: IL-10-rs1554286, -rs1518111, -rs3021094, and -rs1800871 are risk factors for susceptibility to OP.

Morinda officinalis polysaccharide attenuates osteoporosis in rats underwent bilateral ovariectomy by suppressing the PGC-1α/PPARγ pathway.

OBJECTIVE: Osteoporosis (OP) is a widespread disease that causes risks of spine and hip fractures. Morinda officinalis polysaccharide (MOP) shows therapeutic potential in OP. This article intended to understand the mechanism by which MOP impacts bone mineral density (BMD) and serum trace elements in OP rats. METHODS: OP rat models were established by bilateral ovariectomy (OVX). Rats were intragastrically administered with MOP or ZLN005 [the activator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)] since the first day after operation for 8 weeks. Microstructural changes in OP rats were analyzed using micro-computed tomography system. Contents of serum Zn, Cu, Fe, and Mg in rats were measured. Levels of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), GSH, and malondialdehyde (MDA) in rats were determined by Enzyme-linked immunosorbent assay. Protein levels of PGC-1α and peroxisome proliferator-activated receptor γ (PPARγ) in cartilage tissues of rats were determined via Western blotting. RESULTS: MOP enhanced BMD, bone volume per trabecular volume (BV/TV), Tb.N, and Tb.Th and reduced Tb.Sp in the distal femur of OVX rats, elevated levels of serum Cu, Fe, and Mg and contents of SOD, GSH, and GSH-PX and decreased MDA content. Moreover, MOP suppressed the PGC-1α/PPARγ pathway. Activation of PGC-1α partially abolished the action of MOP on ameliorating OP in OVX rats and strengthening anti-oxidation ability. CONCLUSION: MOP mitigated OP in OVX rats by inhibiting the PGC-1α/PPARγ pathway.

IL1R2 polymorphisms and their interaction are associated with osteoporosis susceptibility in the Chinese Han population.

AIMS: Interleukin 1 (IL-1) inhibitory receptor type 2 (IL1R2) serves as a negative regulator of IL-1 signalling and is involved in the pathogenesis of osteoporosis. This study aimed to determine the correlation between IL1R2 polymorphism and osteoporosis susceptibility in the Chinese Han population. METHODS: We recruited 594 osteoporosis patients and 599 healthy controls. Six single nucleotide polymorphisms (SNPs) in IL1R2 were selected for genotyping using the Agena MassARRAY platform. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis with adjustment for age and sex. Linkage disequilibrium analysis was plotted using Haploview v4.2. Multifactor dimension reduction (MDR) was performed to estimate the SNP-SNP interactions of IL1R2 variants. RESULTS: Rs11674595 (OR = 1.86, p = 0.020), rs2072472 (OR = 1.26, p = 0.019) and rs4851527 (OR = 0.78, p = 0.007) were related to the risk of osteoporosis. Moreover, the contribution of IL1R2 polymorphisms to osteoporosis risk was associated with age, sex and body mass index. We found the relationships of Trs11674595 Ars4851527 (OR = 0.80, p = 0.015), Crs11674595 Grs4851527 (OR = 1.22, p = 0.043) and Ars3218977 Grs2072472 (OR = 1.25, p = 0.022) haplotypes to osteoporosis occurrence, and a potential accumulated effect of IL1R2 SNPs (testing accuracy = 0.5783 and cross validation consistency = 10/10) on osteoporosis susceptibility. CONCLUSION: IL1R2 polymorphisms (rs11674595, rs4851527, rs2072472 and rs3218977) may contribute to osteoporosis risk in the Chinese Han population. Our findings may increase our understanding of the effects of IL1R2 polymorphisms on the predisposition to osteoporosis.