ABSTRACT
OBJECTIVE@#To choose the disease-causing gene in a Chinese pedigree with ankylosing spondylitis (AS) by whole-exome sequencing (WES), and provide theory basis for mechanism of disease.@*METHODS@#Clinical data of AS pedigree were collected, including 2 males, the age were 48 and 18 years old, the course of disease were 23 and 4 years. Whole blood genomic DNA of AS was extracted to perform whole exome sequencing, the results were compared with human databases, common variations which had been reported were wiped out, then non synonymous single nucleotide variants(SNVs) from the family members were combined, and candidate genes was selected initially.@*RESULTS@#Totally 80 G data was obtained from AS family with high quality.By comparing results between patient and normal subject, and filtering with number of biological database, the result showed heterozygous mutation of JAK2 gene 12 exon c.1709 A>G (p.Tyr570Cys) may be the potential disease-causing gene. The variant c.1151T>C of MUC3A gene may be one of the causes of intestinal symptoms in the family members.@*CONCLUSION@#It is feasible to find t candidate gene mutations of AS by Exon sequencing. The mutation c.1709 A>G in gene JAK2 identified by whole exome sequencing might be the pathogenic mutation in this AS pedigree.
Subject(s)
Humans , Male , Exome , Mucin-3 , Mutation , Pedigree , Spondylitis, Ankylosing , Exome SequencingABSTRACT
<p><b>OBJECTIVE</b>To observe inhibitory effect of zoledronic acid on polyethylene particle-induced periprosthetic osteolysis model.</p><p><b>METHODS</b>Thirty male adult specific-pathogen-free SD rats (weighted 250 to 300 g) were randomly divided into sham group, model group, and zoledronic acid group, 10 in each group. Modeling were building by titanium screws and polyethylene particles implanted into right femur of rats, sham group and model group were performed hypodermic injection by 0.9% saline with 2 ml/kg, zoledronic acid with 0.1 ml/mg were injected into zoledronic acid group, once a week for 8 weeks. After 8 weeks, right femur specimens were drawn and used to san microstructure of femoral cancellous bone in rats model was examined by Micro-CT, and the images were treated with three-dimension reconstruction and analysis software BMD, BV/TV, Tb.N, Tb.Th, SMI, BS/BV, Tb.Sp and Tb.Pf and other parameters include.</p><p><b>RESULTS</b>According to Micro-CT three-dimensional imaging, BMD in model group was significantly decreased than sham group, bone microstructure damage was serious, bone trabecula changed thinning continuity; while bone microstructure was obviously improved compared with model group and zoledronic acid group. After analyzing Micro-CT parameters of femur microstructure, BMD in model group(0.081±0.020) was significantly decreased than control group(0.160±0.018) and zoledronic acid group(0.125±0.012); BV/TV in model group (10.563±1.070) was obviously lower than control group(27.935±1.834) and zoledronic acid group(14.559±1.258); Tb.N in model group (1.005±0.165) was lower than control group(2.058±0.108) and zoledronic acid group(1.515±0.126); while Tb.Th in model group (0.075±0.016) was decreased than control group(0.158±0.016) and zoledronic acid group(0.124±0.011). Meanwhile, SMI in model group(1.817±0.127) was significantly higher than control group(1.104±0.120) and zoledronic acid group(1.547±0.122); BS/BV in model group(35.784±1.650) was higher than control group(21.506±2.771) and zoledronic acid group(30.399±2.730); Tb.Sp in model group(0.735±0.107) was higher than control group(0.423±0.057) and zoledronic acid group(0.577±0.082), TB.Pf in model group(9.088±1.283) was higher than control group(2.447±0.703) and zoledronic acid group(5.862±1.042).</p><p><b>CONCLUSIONS</b>Zoledronic acid could change bone microstructure of rats to inhibit polyethylene particle-induced bone solution, which provides a scientific basis for prevent bone solution by zoledronic acid as a therapeutic intervention.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect and mechanisim of zoledronate sodium on periprosthetic osteolysis in rat induced by polyethylene particles.</p><p><b>METHODS</b>Total 30 adult male SD rats, weighting from 250 to 300 g, were selected and randomly divided into three groups: blank control group, model control group and zoledronate sodium group respectively, 10 animals for each group. No treatment was performed in the blank control group. In model control group and zoledronate sodium group, the modle of periprosthetic osteolysis in rats were made by implanting polyethylene particles and titanium rods into their right femurs. After operation, rats in zoledronate sodium group were administered with zoledronate sodium (0.1 mg/kg each week) through subcutaneous injection for 8 weeks, then the blood was obtained and all experimental animals were sacrificed to get the right femur specimens. The femur BMD, IL-1β, IL-6, TNF-α, serum TRACP5b and CTX-I were detected.</p><p><b>RESULTS</b>Compared with the model control group, the femur BMD was increased, while IL-1β, IL-6 and TNF-α were all decreased in zoledronate sodium group; the serum TRACP5b and CTX-I level were both reduced in zoledronate sodium group.</p><p><b>CONCLUSION</b>The zoledronate sodium could effectively inhibit periprosthetic osteolysis in rats induced by polyethylene particles, which might be realized by inhibiting the activity of osteoclasts and the expression of IL-1β, IL-6 and TNF-α. It provides a new method to treat periprosthetic osteolysis of the artificial joint prosthesis.</p>