Exploring the Key Genes and Pathways of Osteoarthritis in Knee Cartilage in a Rat Model Using Gene Expression Profiling

PURPOSE: To compare differentially expressed genes (DEGs) mediating osteoarthritis (OA) in knee cartilage and in normal knee cartilage in a rat model of OA and to identify their impact on molecular pathways associated with OA. MATERIALS AND METHODS: A gene expression profile was downloaded from the Gene Expression Omnibus database. Analysis of DEGs was carried out using GEO2R. Enrichment analyses were performed on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway using the Search Tool for the Retrieval of Interacting Genes database (http://www.string-db.org/). Subsequently, the regulatory interaction network of OA-associated genes was visualized using Cytoscape software (version 3.4.0; www.cytoscape.org). RESULTS: In the gene expression profile GSE103416, a total of 99 DEGs were identified. Among them, 76 DEGs (76.77%) were overexpressed, and the remaining 23 DEGs (23.23%) were underexpressed. GO and pathway enrichment analyses of target genes were performed. Using gene-gene interaction network analysis, relevant core genes, including MET, UBB, GNAI3, and GNA13, were shown to hold a potential relationship with the development of OA in cartilage. Using quantitative real-time PCR, the Gna13/cGMP-PKG signaling pathway was identified as a potential research target for therapy and for further understanding the development of OA. CONCLUSION: The results of the present study provide a comprehensive understanding of the roles of DEGs in knee cartilage in relation to the development of OA.

Antibiotic-loaded articulating cement spacers in two-stage revision for infected total knee arthroplasty: individual antibiotic treatment and early results of 21 cases / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To detail our early experience and technique of a modified two-stage reimplantation protocol using antibiotic-loaded articulating cement spacers (ALACSs) for treatment of late periprosthetic infection after total knee arthroplasty (TKA).</p><p><b>METHODS</b>From January 2006 to February 2009, a series of 21 patients (21 knees) with late infected TKAs were treated by radical debridement and removal of all components and cement, and then articulating spacers were implanted using antibiotic-impregnated bone cement. For this purpose, 4 g vancomycin powder was mixed with per 40 g cement. Graduated knee motion and partial weight bearing activity were encouraged in the interval period. Each patient received an individual systemic organism-sensitive antimicrobial therapy for 4.9 (range, 2-8) weeks followed by a second-stage TKA revision. All the patients were regularly followed up using the American Knee Society Scoring System.</p><p><b>RESULTS</b>Each case underwent a successful two-stage exchange and had infection eradicated, none had recurrent infection after an average of 32.2 (range, 17-54) months of follow-up. Preoperatively, the mean knee score was 53.5 points, function score was 27.3 points, pain score was 25.7 points, range of motion (ROM) was 82.0 degree extensor lag was 2 degree Between stages, the mean knee score was increased to 61.3 points, function score to 45 points, pain score to 35 points, ROM to 88.2 degree and extensor lag to 3.4 degree At final follow-up, the mean knee score was further increased to 82.1 points, function score to 74.5 points, pain score to 42.1 points, ROM to 94.3 degree and knee extension lag to 1.9 degree The interval period was 11.5 (range, 6-32) weeks. The amount of bone loss was unchanged between stages. No patient developed noticeable dysfunction of the liver or kidney or other complications such as impaired wound healing, deep venous thrombosis, pulmonary embolism, cerebrovascular accidents, etc.</p><p><b>CONCLUSIONS</b>Treating infected TKA with ALACS avoids spacer-related bone loss, preserves knee function between stages, and eradicates infection effectively without significant complications. The early clinical results are inspiring. The authors believe that radical and repeated (if needed) debridement, individual application of systemic antibiotics, and reasonable timing judgement upon the secondary revision are all key factors related to a successful outcome with two-stage reimplantation procedure for infected TKA.</p>

Management of postoperative pain after total knee arthroplasty / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate causes and clinical management of postoperative pain after total knee arthroplasty (TKA).</p><p><b>METHODS</b>From January 2004 to June 2009, 41 patients (44 knees) with knee pain post TKA were treated. There were 9 male and 32 female patients aging from 51 to 84 years with a mean of 63.5 years. The diagnosis followed to Brown diagnostic system. One case of extraarticular pain was complex regional pain syndrome type 1 (CRPS-1) and underwent conservative treatment, the remaining 5 cases were treated by surgery. Three cases of joint instability, 1 case of patellar baja, 2 cases of soft tissue impingement caused by overhang of the prosthesis, 1 case of popliteal tendon impact underwent conservative treatment, the other 27 cases underwent surgical intervention. The patients were followed up and the Knee Society Score (KSS) knee score, pain visual analog scale (VAS) score were recorded.</p><p><b>RESULTS</b>Forty-one cases were followed up for 1 to 6 years. At the last time of follow-up, the 5 cases received surgical treatment to extra-articular pain showed VAS score as 2.5 ± 0.2, KSS clinical and functional score as 92.8 ± 2.6 and 89.0 ± 3.4. There was significantly difference compared with preoperative (P < 0.05). One case of CRPS-1 performed conservative treatment, the therapy was effective. In the infected 12 cases of intra-articular pain, 1 case received amputation, 3 cases received antibiotic bone cement insert, 8 cases received two stage revision. All infections were cured, and VAS score was 3.8 ± 0.2, KSS clinical score was 88.3 ± 4.6, function score was 85.0 ± 4.6 postoperatively, with significantly difference compared with preoperative (P < 0.05). In the 8 cases received conservative treatment in non-infected group, at the last time of follow-up, VAS score was 4.5 ± 0.4, KSS clinical and functional score was 85.4 ± 4.2 and 84.2 ± 2.3, with significantly difference compared with preoperative (P < 0.05). Fifteen cases underwent surgical treatment, at the last time of follow-up, VAS score was 3.4 ± 0.1, KSS clinical and functional score was 86.6 ± 5.4 and 87.1 ± 2.4, with significantly difference compared with preoperative (P < 0.05).</p><p><b>CONCLUSIONS</b>Patients with knee pain post TKA need systematic assessment to identify the causes. Appropriate treatment due to the positive diagnosis generally lead to satisfactory results, surgical intervention with indefinite causes is strictly prohibited.</p>

Effect of posterior condylar offset on knee flexion after high-flex posterior-stabilized total knee arthroplasty / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the effect of the posterior condylar offset (PCO) on intra- and post-operative knee flexion after total knee arthroplasty (TKA) using a high-flex posterior-stabilized (PS) fixed-bearing prosthesis and to discuss it's importance in femoral prosthesis design.</p><p><b>METHODS</b>The clinical and radiographic materials of 100 consecutive patients (100 knees) were prospectively studied, including 50 men and 50 women, who had undergone primary NexGen LPS-Flex TKAs for end-stage osteoarthritis. All operations were performed by a single surgeon using the same operative technique between March 2005 and October 2006. Pearson's regression analysis was used to assess the relationship between the difference in the pre- and post-operative PCO on true lateral radiographs and the change in knee range of flexion (ROF) under non-weight-bearing conditions.</p><p><b>RESULTS</b>The decrease of the corrected PCO was (3.4 ± 3.3) mm compared with the preoperative value, the restoration of PCO was better in male than female [female (-5.4 ± 3.1) mm vs. male (-1.5 ± 2.0) mm, P < 0.05]. The difference in the corrected PCO after PS TKA demonstrated significantly correlated with the change in 2 years postoperative ROF in male and female, respectively (P < 0.05). While no statistically correlation was observed in the overall group (P > 0.05). Intraoperatively, the difference in the corrected PCO was significantly correlated with the change in ROF in male, female, and the overall group, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>Restoration of PCO plays an important role in the optimization of knee flexion after high-flex PS TKA. Femoral components based on Caucasian anatomic characteristics could not match the native anatomy of distal femurs of Chinese population especially female Chinese. Rotated resection of distal femur with anterior referencing technique usually leads to a decreased PCO and therefore reduces maximal obtainable flexion. Sexual dimorphism in humans and anatomic variations in various ethnic groups should be seriously considered in total knee prosthesis design.</p>