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Effect of OPG gene mutation on protein expression and biological activity in osteoporosis.

ABSTRACT: The effect of an osteoprotegerin (OPG) gene mutation was investigated on its protein expression and biological activity in osteoporosis. The pcDNA3.0-OPG plasmid or wild-type plasmid were transfected into HEK293 cells. Osteoclast tartrate-resistant acid phosphatase (TRAP) staining and counting were then performed, and the expression of genes related to osteoclast differentiation and activation were measured by RT-PCR. The wild-type or mutant-type OPG at concentrations of 0, 10, 20, 50 and 100 ng/ml were added respectively to RAW264.7 cells and incubated for 24 h. The viability of cells treated with the wild-type and mutant-type OPG at a concentration of 100 ng/ml was still over 99%, which indicated that the wild-type and mutant-type OPG at this concentration had no cytotoxic effect on RAW264.7 cells. The number of TRAP-positive cells decreased with increasing concentration of wild-type or mutant-type OPG. At the concentrations of 20, 50 and 100 ng/ml, the inhibitory effect of wild-type OPG was significantly higher than that of mutant-type OPG (p<0.05). Both mutant-type and wild-type OPG inhibited the bone resorption activity of osteoclasts, and the inhibitory effect of wild-type OPG was significantly higher than that of mutant-type OPG at the concentrations of 20, 50 and 100 ng/ml (p<0.05). The levels of TRAP and RANK mRNA in the wild-type OPG treatment group were significantly lower than those in the control group, while the levels of TRAP and RANK mRNA in the mutant-type OPG treatment group were significantly lower than those in the wild-type group (p<0.05). The genetic mutation did not affect the protein expression levels of OPG, but inhibited the normal activity of OPG.

SUBMITTER: Qin S

PROVIDER: S-EPMC5526059 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:ObjectiveThis study aimed to explore the correlation between the SRY-related high-mobility-group box gene 4 (SOX4) 3' untranslated region (UTR) single nucleotide polymorphism (SNP) and osteoporosis susceptibility.MethodsThe study recruited 330 osteoporosis patients (the case group) and 330 non-osteoporosis patients (the control group) in Sichuan Chengdu First People's Hospital and Zibo Central Hospital from August 2016 to August 2019. Sanger sequencing was used to analyze the genotypes of SOX4 gene rs79958549, rs139085828, and rs201335371 loci. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the SOX4 gene rs79958549, rs139085828, and rs201335371 loci and the clinical characteristics of the subjects.ResultsThe risk of osteoporosis in the carriers of A allele at SOX4 rs79958549 was 5.40 times that in the carriers of the G allele (95% CI 3.25-8.96, P < 0.01). The risk of osteoporosis in the carriers of the A allele at SOX4 rs139085828 was 1.68 times that in the carriers of the G allele (95% CI 1.45-1.85, P < 0.01). The risk of osteoporosis in the carriers of the T allele at SOX4 rs201335371 was 0.54 times that in the carriers of the C allele (95% CI 0.43-0.69, P < 0.01). The SOX4 gene rs79958549, rs139085828, and rs201335371 A-A-C haplotype (OR = 5.14, 95% CI 2.45-10.57, P < 0.01) were associated with increased risk of osteoporosis and G-G-T haplotype was significantly associated with decreased risk of osteoporosis (OR = 0.48, 95% CI 0.38-0.62, P < 0.01). The interaction among the factors of sex, smoking, drinking, rs79958549, rs201335371 was the best model for osteoporosis prediction, and the risk for osteoporosis in 'high-risk combination' was 2.74 times that of 'low-risk combination' (95% CI 1.01-7.43, P = 0.04). Multiple logistic regression analysis revealed that the risk factors for osteoporosis were BMD (OR = 5.85, 95% CI 2.88-8.94, P < 0.01), T score (OR = 8.54, 95% CI 5.66-10.49, P < 0.01), Z score (OR = 3.77, 95% CI 2.15-8.50, P < 0.01), rs79958549 SNP (OR = 6.92, 95% CI 3.58-8.93, P < 0.01), and rs139085828 SNP (OR = 2.36, 95% CI 1.85-4.27, P < 0.01). The protective factor for osteoporosis was rs201335371SNP (OR = 0.48, 95% CI 0.32-0.75, P < 0.01).ConclusionThe SOX4 gene SNPs rs79958549, rs139085828, and rs201335371 loci were significantly associated with osteoporosis risk.

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Effect of OPG gene mutation on protein expression and biological activity in osteoporosis.

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