Chongru He

Changes in gene expression profiles of the hip joint ligament of patients with ankylosing spondylitis revealed by DNA chip.

To investigate the pathogenesis of abnormal ossification of the hip ligament in patients with ankylosing spondylitis (AS) by comparing gene expression profiles of the hip ligament in patients with AS to those in normal persons using DNA microarray technology, we studied 18 patients with AS (case group) who underwent total hip arthroplasty in our department from March 1, 2009 to January 31, 2010 and compared them with 6 patients with femoral neck fracture (control group) who underwent total hip replacement. We screened the first five patients in each group with the HumanWG-6 v3.0 Expression BeadChip. Compared to the control group, 519 genes in the case group showed statistically significant differences. Among these, there were 238 upregulated genes and 196 downregulated genes. Gene Ontology (GO) classification showed that differential genes in the hip joint ligaments of patients with AS were involved in immunity, cell adhesion, membrane transport, sugar metabolism, polysaccharide synthesis and metabolism, and cell motility. The Kyoto Encyclopedia of Genes and Genomes classification showed that these differential genes were involved in B cell receptor signaling pathways, adherens junction, protein export, fructose and mannose metabolism, T cell receptor signaling pathways, keratin sulfate biosynthesis, N-glycan biosynthesis, and regulation of the actin cytoskeleton. We tested 2 genes from the screened differential genes in 18 case patients and 6 control cases using real-time polymerase chain reaction. The results demonstrated that the expression of the B4GALT3 gene in the case group was 15.32 times higher than that in the control group (P < 0.01), and the expression of the RBP5 gene in the case group was 4.09 times higher than that in the control group (P < 0.01). This conformed to the microarray analysis. Our preliminary data suggest that differential gene expression in patients with AS includes the immune system, intracellular or extracellular signaling pathway, and bone matrix biosynthesis pathway, which might play important roles in hip joint ligament ossification.

Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review)

The study of ankylosing spondylitis (AS) has made significant progress over the last decade. Genome-wide association studies have identified and further substantiated the role of susceptibility genes outside the major histocompatibility complex locus. However, human leukocyte antigen (HLA)-B27 has been suggested to be important in the pathogenesis of AS, contributing to ~20.1% of AS heritability. The current review will present the classical and non-classical forms of HLA-B27, as well as their pathogenic roles, and further discuss the hypotheses regarding the potential pathogenesis of AS. In addition, the association between the pathogenic role of HLA-B27 and inflammatory indexes, including the interleukin-23/−17 axis will be investigated to provide novel insights into the pathogenesis of AS. The aim of the present review is to provide an update of the current research into the pathogenesis of AS, and provide a comprehensive description of the pathogenic role of HLA-B27 in AS.

Early Failure of the Durom Prosthesis in Metal-on-Metal Hip Resurfacing in Chinese Patients

Hip resurfacing (HR) is being used increasingly as an alterative to total hip arthroplasty in osteonecrosis (ON) and ankylosing spondylitis (AS) of the hip. We performed 141 consecutive HR arthroplasties in 111 patients comprising 3 etiology groups: ON, AS, and osteoarthritis (OA). After retrospective study of retrieved components, we hypothesized that the main reason for revision was femoral loosening in the ON group (4 of 46 hips; 8.7%) and femoral-neck fracture in the AS group (3 of 58 hips; 5.2%). Necrotic areas were seen on femoral heads retrieved from patients with femoral loosening, whereas femoral heads were fixed tightly to components in patients with femoral-neck fractures. Etiology may be an important risk factor for postoperative complications.

Differentially expressed mRNAs, lncRNAs, and miRNAs with associated co-expression and ceRNA networks in ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation and pathological osteogenesis. However, the genetic etiology of AS remains largely unknown. This study aimed to explore the potential role of coding and noncoding genes in the genetic mechanism of AS. Using microarray analyses, this study comprehensively compared lncRNA, microRNA, and mRNA profiles in hip joint ligament tissues from patients with AS and controls. A total of 661 lncRNAs, 574 mRNAs, and 22 microRNAs were differentially expressed in patients with AS compared with controls. Twenty-two of these genes were then validated using real-time polymerase chain reaction. Gene ontology and pathway analyses were performed to explore the principal functions of differentially expressed genes. The pathways were involved mainly in immune regulation, intercellular signaling, osteogenic differentiation, protein synthesis, and degradation. Gene signal transduction network, coding–noncoding co-expression network, and competing endogenous RNA expression network were constructed using bioinformatics methods. Then, two miRNAs, miR-17-5p and miR-27b-3p, that could increase the osteogenic differentiation potentials of ligament fibroblasts were identified. Finally, differentially expressed, five lncRNAs, four miRNAs, and five mRNAs were validated using quantitative real-time polymerase chain reaction. These results suggested that mRNAs, lncRNAs, and microRNAs were involved in AS pathogenesis. The findings might help characterize the pathogenesis of AS and provide novel therapeutic targets for patients with AS in the future.

Comparison of Blood Loss After Total Hip Arthroplasty Between Ankylosing Spondylitis and Osteoarthritis

BACKGROUND This study was conducted to compare the blood loss during primary total hip arthroplasty (THA) between ankylosing spondylitis (AS) and hip osteoarthritis (OA). METHODS We reviewed 120 THAs in 68 patients comprising 3 groups: AS with total bony ankylosis of the hips (ASB), AS with stiff hips (ASS), and OA. Demographics, perioperative laboratory values, intraoperative data, blood loss, transfusion rate, transfusion reactions, surgical complications, hospitalization cost, and length of stay (LOS) were collected and analyzed among ASB, ASS, and OA groups. RESULTS The patients of the ASB and ASS groups were much younger and thinner than those of the OA group. There were no significant differences in the preoperative values of activated partial thromboplastin time, prothrombin time, and international normalized ratio among the 3 groups (all P > .05). The intraoperative blood loss, volume of drainage, hidden blood loss, transfusion rate, transfusion reactions, and hospitalization cost in the ASB group were significantly higher than in the other 2 groups, although not significantly different between the ASS and OA groups (P > .05). CONCLUSION Both AS and OA can cause hyperosteogeny to the hips, but ASB patients have more serious symptoms in their affected hips. This may cause more blood loss in THA surgery because of bone surface bleeding. The reason that ASB patients suffered more blood loss may be related to the high difficulty and long duration of the operation.

Mutations in the B30.2 domain of pyrin and the risk of ankylosing spondylitis in the Chinese Han population: a case-control study.

Ankylosing spondylitis (AS) and familial Mediterranean fever (FMF) are a common autoimmune disease and a classic autoinflammatory disease, respectively. Mediterranean fever (MEFV) encodes the pyrin protein and is the causal disease gene in FMF. This protein is an important regulator of innate immunity and may play a key role in the development of AS. To identify the mutations in the B30.2 domain of pyrin and to uncover the relationships between these mutations and AS risk in the Chinese Han population, we extracted genomic DNA from the peripheral blood of 200 AS patients and 200 matched controls and performed polymerase chain reactions (PCRs) and direct sequencing on those samples. Statistical analysis indicated that only Met694Val (rs61752717) in the B30.2 domain of pyrin could affect the risk of AS (P = 0.042; odds ratio [OR] = 5.103; 95% confidence interval [CI] = 1.111-23.437 for the model of Met (M) vs. Val (V), P = 0.040; OR = 5.211; 95% CI = 1.127-24.091 for the model of MM vs. MV+VV). Moreover, M694V is significantly associated with a higher level of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in AS patients. Our results are the first to suggest that the M694V allele of the pyrin was associated with AS risk in the Chinese Han population and that this mutation may be associated with the inflammatory response in the development of AS.

Annexin A2, up-regulated by IL-6, promotes the ossification of ligament fibroblasts from ankylosing spondylitis patients

BACKGROUND Annexin A2, a calcium-dependent phospholipid binding protein, is involved in osteogenesis. The objective of the present study was to explore the expression of Annexin A2 in spinal ligament tissues (LT) of ankylosing spondylitis (AS) patients and determine its pathological functions. METHODS mRNA and protein expression of Annexin A2 was detected by real-time PCR and Western blotting, respectively. Interleukin-6 (IL-6) concentration in serum was assessed by enzyme linked immunosorbent assay. Alkaline phosphatase (ALP) activity was measured with ALP activity kit on a microplate reader. RESULTS mRNA and protein expression of Annexin A2 in LT, and IL-6 concentration in serum were significantly increased in AS patients. Moreover, exogenous IL-6 treatment significantly up-regulated Annexin A2 expression and ALP activity. Silencing of Annexin A2 expression significantly ameliorated IL-6-induced ossification of fibroblasts from AS patients, as indicated by ALP activity, expression of proteins associated with osteogenic differentiation, including bone morphogenetic protein-2, osteocalcin and osterix, and the ratio of osteoprotegerin to receptor activator of NF-κB ligand. Further MEK inhibitor experiments suggested that Annexin A2 may exert its function through extracellular signal-related kinase pathway. CONCLUSIONS Annexin A2, up-regulated by IL-6, may promote ligament ossification of AS patients.

Simplified Chinese version of hip and knee replacement expectations surveys in patients with osteoarthritis and ankylosing spondylitis: cross-cultural adaptation, validation and reliability

BackgroundThe Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) and Knee Replacement Expectations Survey (HSS-TKRES) are widely used tools developed to assess patients’ preoperative expectations for total hip and knee arthroplasty. This study aimed to translate and adapt the HSS-THRES and HSS-TKRES into Chinese versions (SC-THRES/TKRES) and evaluate their psychometric properties in patients with osteoarthritis (OA) and ankylosing spondylitis (AS).MethodsPatients scheduled for total hip (104 hip OA and 51 AS) or knee replacements (101 knee OA) were recruited in this study. Confirmatory Factor Analysis (CFA) was used to evaluate structural validity. The internal consistency was assessed by the Cronbach’s α coefficient. The intraclass correlation coefficient (ICC) was used to assess test-retest reliability. The construct validity was analyzed by evaluating the correlations between SC-THRES/TKRES and the Expectation WOMAC. The correlations with the Expectation WOMAC were tested against our hypotheses. We additionally compared preoperative expectations of AS patients to those of hip OA patients.ResultsThe results of CFA for the SC-THRES and SC-TKRES demonstrated good fit. The results for the SC-THRES/TKRES revealed good test-retest reliability and good internal consistency (AS: ICC = 0.893, Cronbach’s α = 0.815; hip OA: ICC = 0.878, Cronbach’s α = 0.814; knee OA: ICC = 0.806, Cronbach’s α = 0.808). The correlations between the SC-THRES/TKRES and the Expectation WOMAC were moderate (0.541 for AS, 0.490 for hip OA and 0.465 for knee OA), which were consistent with the hypotheses.ConclusionThe SC-THRES/TKRES are reliable, valid for the evaluation of Chinese patients with OA and AS undergoing total hip and knee arthroplasty. The surveys can be used as part of preoperative assessments. Meanwhile, additional research is needed to replicate these findings and to assess the content validity in a larger sample.

Gentamicin coating of nanotubular anodized titanium implant reduces implant-related osteomyelitis and enhances bone biocompatibility in rabbits

Titanium and titanium alloy are widely used as orthopedic implants for their favorable mechanical properties and satisfactory biocompatibility. The aim of the present study was to investigate the antibacterial effect and bone cell biocompatibility of a novel implant made with nanotubular anodized titanium coated with gentamicin (NTATi-G) through in vivo study in rabbits. The animals were divided into four groups, each receiving different kinds of implants, that is, NTATi-G, titanium coated with gentamicin (Ti-G), nanotubular anodized titanium uncoated with gentamicin (NTATi) and titanium uncoated with gentamicin (Ti). The results showed that NTATi-G implant prevented implant-related osteomyelitis and enhanced bone biocompatibility in vivo. Moreover, the body temperature of rabbits in NTATi-G and Ti-G groups was lower than those in Ti groups, while the weight of rabbits in NTATi-G and Ti-G groups was heavier than those in NTATi and Ti groups, respectively. White blood cell counts in NTATi-G group were lower than NTATi and Ti groups. Features of myelitis were observed by X-ray films in the NTATi and Ti groups, but not in the NTATi-G and Ti-G groups. The radiographic scores, which assessed pathology and histopathology in bone tissues, were significantly lower in the NTATi-G and Ti-G groups than those in the NTATi and Ti groups, respectively (P<0.05). Meanwhile, explants and bone tissue culture demonstrated significantly less bacterial growth in the NTATi-G and Ti-G groups than in the NTATi and Ti groups, respectively (P<0.01). The bone volume in NTATi-G group was greater than Ti-G group, and little bone formation was seen in NTATi and Ti groups.