Clinical, Radiographic, and MRI Evaluation of All-Inside Medial Meniscus Posterior Root Repair via Suture Fixation to the Posterior Cruciate Ligament Versus Partial Meniscectomy: Results at 3-Year Follow-up.

Background: Medial meniscus posterior root tears (MMPRTs) disrupt the integrity and hoop tension of the meniscus, leading to cartilage degeneration and accelerated osteoarthritis (OA) progression. The management of patients with MMPRT is controversial, and the efficacy of different treatment options is unclear. Purpose: To compare the clinical, radiographic, and magnetic resonance imaging (MRI) outcomes of patients with MMPRT between trans-posterior cruciate ligament (trans-PCL) all-inside repair and partial meniscectomy. Study Design: Cohort study; Level of evidence, 3. Methods: We identified patients with MMPRT who underwent trans-PCL all-inside repair (group AR) or partial meniscectomy (group PM) between 2015 and 2019 at a single institution. The trans-PCL all-inside repair was performed by suturing the torn meniscus root to the PCL fibers. Patient-reported outcomes as well as radiographic and MRI outcomes were collected at baseline and final follow-up. Clinical failure was defined as conversion to total knee arthroplasty (TKA), and Kaplan-Meier survival analysis was used to investigate the survival rates of patients with different surgical procedures. Results: Included were 29 patients in group AR and 31 patients in group PM (mean age, 62.69 and 60.68 years, respectively; mean follow-up, 2.91 ± 1.33 and 3.45 ± 1.50 years, respectively). There were no differences in baseline patient characteristics between the groups. All patient-reported outcome scores improved significantly in both groups at the final follow-up. When we compared final outcomes between the groups, group AR had less joint space narrowing (P = .010), less Kellgren-Lawrence OA grade progression (P = .002), and less medial meniscal extrusion (MME; P = .002) than group PM. In addition, group AR showed less progression of bone marrow lesions and cartilage lesions (P < .05) than group PM. The rate of conversion to TKA was 6.90% in group AR and 29.0% in group PM. The 5-year survival rates in the AR and PM groups were 82.6% and 59.8%, respectively (P = .153). Conclusion: Trans-PCL all-inside repair for MMPRTs was associated with greater improvement in clinical function, better radiographic results, less MME and cartilage degeneration, and a lower rate of subsequent TKA compared with partial meniscectomy.

Multidisciplinary Guidelines for the Rational Use of Topical Non-Steroidal Anti-Inflammatory Drugs for Musculoskeletal Pain (2022).

(1) Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are one of the primary drugs for treating musculoskeletal pain. However, there are currently no evidence-based recommendations about drug selection, drug administration, drug interactions, and use in special populations or other pharmacology-related content of such medications. To this end, the Chinese Pharmaceutical Association Hospital Pharmacy Professional Committee developed multidisciplinary guidelines on using topical NSAIDs to treat musculoskeletal pain. (2) Methods: The guidelines development process followed the World Health Organization guideline development handbook, the GRADE methodology, and the statement of Reporting Items for Practice Guidelines in Healthcare. The guideline panel used the Delphi method to identify six clinical questions to be addressed in the guidelines. An independent systematic review team conducted a systematic search and integration of evidence. (3) Results: Based on the balance between the benefits and harms of an intervention, the quality of the evidence, patient preferences and values, and resource utilization, the guideline panel developed 11 recommendations and nine expert consensuses on using topical NSAIDs to treat acute and chronic musculoskeletal pain. (4) Conclusions: Based on the effectiveness and overall safety of topical NSAIDs, we recommend patients with musculoskeletal pain use topical NSAIDs and suggest high-risk patients use topical NSAIDs, such as those with other diseases or receiving other concurrent treatments. The evidenced-based guidelines on topical NSAIDs for musculoskeletal pain incorporated a pharmacist perspective. The guidelines have the potential to facilitate the rational use of topical NSAIDs. The guideline panel will monitor the relevant evidence and update the recommendations accordingly.

Trans-Posterior Cruciate Ligament All-Inside Root Repair Versus Partial Meniscectomy for Medial Meniscus Posterior Root Tears: Comparison of Semiquantitative and Quantitative MRI Outcomes in Cartilage Degeneration and Osteoarthritic Progression.

OBJECTIVE: To perform conventional, morphological, and T2 mapping compositional MRI imaging to assess the cartilage degeneration and osteoarthritic progression in patients with medial meniscus posterior root tears (MMPRTs) who underwent trans-posterior cruciate ligament (PCL) all-inside repair or partial meniscectomy. DESIGN: Patients with MMPRTs after trans-PCL all-inside repair (group AR) or partial meniscectomy (group PM) between 2015 and 2018 were retrospectively identified. Preoperative and postoperative conventional MRI were collected to assess medial meniscus extrusion (MME) and the whole-organ magnetic resonance imaging score (WORMS). Postoperative morphological MRI and T2 mapping compositional MRI were collected to evaluate the quantitative cartilage thickness/volume and cartilage composition. RESULTS: The final cohort consisted of 21 patients in group AR and 22 patients in group PM, with no differences in demographic data and baseline patient characteristics between the 2 groups. Group AR demonstrated less progression of articular cartilage wear (P < 0.05) and decreased meniscal extrusion (P = 0.008) than group PM at the final follow-up. In addition, group AR demonstrated less extracellular matrix degeneration in the cartilage subregion of the medial compartment (P < 0.05) than group PM with lower T2 relaxation times in the superficial layer of the articular cartilage. CONCLUSION: Trans-PCL all-inside repair of MMPRTs could delay the initial cartilage deterioration and morphological cartilage degeneration compared with partial meniscectomy. However, the amount of residual meniscal extrusion is clinically important, and an improved root repair fixation method should be investigated.

The role of knee arthroscopy in managing common soft tissue complications after total knee arthroplasty: a retrospective case series study.

BACKGROUND: To investigate the feasibility, safety and therapeutic efficacy of arthroscopy in managing the 3 most common soft tissue complications, peripatellar impingement (PI), arthrofibrosis (AF) and generalized synovitis (GS), after total knee arthroplasty (TKA). METHODS: A retrospective review of patients undertaking arthroscopy for PI, AF and GS was conducted. Outcome measures included complications, postoperative range of motion (ROM), Knee Society Score (KSS) and rates of symptom recurrence, prosthesis revision. Intraoperative findings and surgical procedures were also recorded. Paired t test, Fisher's exact test, Kruskal-Wallis test and post hoc analysis with Bonferroni correction were used for statistical evaluation. RESULTS: A total of 74 patients, including 35 patients with peripatellar impingement, 25 patients with arthrofibrosis and 14 patients with generalized synovitis, with a mean age of 66.1 ± 7.9 years, were analysed. The mean follow-up (FU) duration was 81.3 ± 40.6 months. All patients underwent arthroscopic surgery safely without intraoperative complications. However, there were 4 postoperative complications, including 1 acute myocardial infarction and 3 periprosthetic joint infections. Overall, patients acquired improvements in ROM from 81.7 ± 23.1° to 96.8 ± 20.5° (p < 0.05), in KSS knee score from 64.2 ± 9.6 to 78.7 ± 12.1 (p < 0.05) and in KSS function score from 61.1 ± 7.4 to 77.3 ± 12.2 (p < 0.05) postoperatively. Patients in all 3 groups had improvements in ROM (p < 0.05), KSS knee score (p < 0.05) and KSS function score (p < 0.05). The overall recurrence rate was 22.9% (95% confidence interval (CI) 15.1-34.9%), and the overall revision rate was 14.9% (95% CI 8.6-25.6%). There were significant differences in both the symptom recurrence and prosthesis revision rates among the groups (p < 0.05). The PI group had a significantly lower symptom recurrence rate (11.4%, 95% CI 4.5-28.7%) and revision rate (8.6%, 95% CI 2.9-25.3%) (p < 0.017), while the GS group had a significantly higher recurrence rate (42.9%, 95% CI 23.4-78.5%) and revision rate (35.7%, 95% CI 17.6-72.1%) (p < 0.017). CONCLUSIONS: In the setting of symptomatic TKA, although carrying certain risks for PJI and other complications, arthroscopic intervention could be feasible and provide clinical improvement in most cases at an average of 81.3 months follow-up. Patients with PI had the best outcomes, while patients with GS had the worst outcomes. LEVEL OF EVIDENCE: Level IV.

Effects of cell phenotype and seeding density on the chondrogenic capacity of human osteoarthritic chondrocytes in type I collagen scaffolds.

OBJECTIVE: Matrix-associated autologous chondrocyte implantation (MACI) achieves good clinical efficacy in young patients with focal cartilage injury; however, phenotypic de-differentiation of chondrocytes cultured in monolayer and the treatment of older OA patients are still challenges in the field of cartilage tissue engineering. This study aimed to assess the in vitro re-differentiation potential and in vivo chondrogenic capacity of human OA chondrocytes inoculated into collagen I scaffolds with different cellular phenotypes and seeding densities. METHODS: OA chondrocytes and articular chondrocyte-laden scaffolds were cultured over 2 weeks in in vitro. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and histological staining were used to detect the mRNA expression profiles and extracellular matrix secretion of chondrocyte-specific markers. OA chondrocyte-laden collagen I scaffolds with different cellular phenotypes, and seeding densities were implanted into SCID mice over 4 weeks to evaluate the chondrogenic capacity in vivo. RESULTS: Increased COL2a1, ACAN, COMP, SOX9, and BMP2 expression levels and decreased COL1a1, VCAN, MMP13, and ADAMTS5 amounts were observed in OA chondrocytes seeded in collagen I scaffolds; Implantation of phenotypically superior OA chondrocytes in collagen I scaffolds at high density could improve the chondrogenic capacity of human OA chondrocytes, as confirmed by RT-qPCR assessed gene expression patterns in vitro and histological evaluation in vivo. CONCLUSIONS: Freshly isolated chondrocytes from OA patients could be a source of replacement for articular chondrocytes being commonly used in MACI. Implantation of phenotypically superior OA chondrocytes in collagen I scaffolds at high density could be a promising tool for the treatment of elderly OA patients.

Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVES: To evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety. DESIGN: Double-blind, pragmatic, randomised, placebo-controlled trial. SETTING: Four tertiary hospitals in China. PARTICIPANTS: 246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA). INTERVENTIONS: Patients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption. RESULTS: The cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group. CONCLUSIONS: The sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (ID: NCT02198924).

PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis.

BACKGROUND: The Cadherin-11 and PI3K/Akt pathway are increasingly recognized as the potential therapeutic target of osteoarthritis (OA) synovitis. The study aimed to investigate the role of PI3K/Akt signaling pathway in the expression of Cadherin-11 and migration and invasive capacity of fibroblast-like synoviocytes (FLS) of OA patients under stimulation of TNF-α and to explore the effect of the PI3K/Akt inhibitor and Cadherin-11 antibody in the therapy of the collagenase-induced osteoarthritis (CIOA) mice. METHODS: FLS were primarily cultured from synovium of osteoarthritic patients during total knee arthroplasty. Under the simulation of TNF-α, with or without PI3K/Akt inhibitor LY294002, Cadherin-11 expression was detected by real-time PCR and Western blot, as well as the migration and invasive capacity changes of OA FLS. Cadherin-11 antibody was injected intraarticularly or LY294002 was injected intraperitoneally in CIOA mice to evaluate the changes of synovitis score, cartilage damage, and Cadherin-11 expression. RESULTS: TNF-α stimulation increased Cadherin-11 expression at mRNA and protein level in OA FLS and also increased the phosphorylation-dependent activation of Akt. PI3K inhibitor LY294002 attenuated TNF-α-induced overexpression of Cadherin-11 and decreased the invasive capacity of OA FLS. Intraperitoneal injection of PI3K inhibitor LY294002 could decrease the Cadherin-11 protein expression in synovium of CIOA mice, although it has no significant inhibitory effect on synovitis and cartilage damage. Intraarticular injection of Cadherin-11 antibody attenuated the synovitis and cartilage damage in the CIOA joints and decreased Cadherin-11 expression in the synovial lining. CONCLUSIONS: PI3K/Akt pathway was associated with TNF-α-induced activation of OA FLS, which may involve in the pathogenesis of osteoarthritis. Anti-Cadherin-11 therapy in CIOA mice could attenuate the pathological changes of OA joints.

The diagnosis and arthroscopic treatment of angioleiomyoma presenting loose body in the knee joint: two case reports.

BACKGROUND: Angioleiomyoma is a very rare benign solitary soft tissue neoplasm originating from smooth muscle layer of blood vessels. The tumor is usually located in the subcutis or the superficial fasciae, but less often in the deep fasciae, especially rare in the knee joint cavity. Diagnosis is frequently delayed or misdiagnosed as loose body or anterior knee pain because of its rare occurrence and poor awareness of physicians. Few studies have presented intra-articular angioleiomyoma and such cases become rarer and more difficult to diagnose when it presents as loose body. CASE PRESENTATION: Two patients, a middle-aged man and an old woman, presented to our outpatient clinic with persistent anterior knee pain and both of them suffered from a solitary mass in the right knee that had slowly enlarged. One of two patients showed negative in the routine radiographic imaging and the other showed a "loose body" beside the lateral femoral condyle in the knee. MRI showed both a well-demarcated intra-articular mass of isointense signal to muscle on T1-weighted images and heterogeneous intensity on T2-weighted images. Their tumors were excised under arthroscopy finally, with the pathological results revealed vascular leiomyomas. They both recovered well with pain free after operation and no signs of recurrence were seen at the 7-year follow-up. CONCLUSIONS: This case report illustrates the atypical locations of angioleiomyoma in the knee joint should arouse our attention and be included in the differential diagnosis of nodular lesions mimicking loose bodies.

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.

INTRODUCTION: Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. METHODS AND ANALYSIS: This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. ETHICS AND DISSEMINATION: Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. TRIAL REGISTRATION NUMBER: NCT02198924.

[The mid-term follow-up of revision total knee athroplasty].

OBJECTIVE: To summarize the mid-term follow-up results of revision of total knee arthroplasty and compare the different strategies for infective revisions. METHODS: All of 45 patients (47 operated knees) lived in Beijing were treated from April 1989 to October 2010 in Arthritis Clinic and Research Center, Peking University People's Hospital. There were 6 male and 39 female patients, who aged from 31 to 77 years (mean (62 ± 11) years). The function of knee, satisfaction and imaging then were compared retrospectively. American Knee Society Scores (KSS), Western Ontario & McMaster University Osteoarthritis Index (WOMAC), the medical outcomes study item short form health survey (SF-36) scales and satisfaction/pain visual analogue scales (VAS) of patients were evaluated. The patients were divided into infection group (33 patients, 34 knees) and non-infection group (12 patients, 12 knees) according to the indication of revision of total knee arthroplasty and compared by t-tests. RESULTS: The time from operation to follow-up was 1 year and 2 months to 17 years. The mid-term follow-up time was 8 years 3 months. There were significant improvements of KSS clinical and function scores (from 66.9 ± 28.0 and 44.4 ± 37.6 to 25.4 ± 24.2 and 10.0 ± 24.8, t = 7.043 and 3.797, both P = 0.001). Patients of infection group had lower KSS clinical and function scores than non-infection group before operation, and lower Society Function (t = 2.225, 3.520 and 2.885, P = 0.035, 0.002 and 0.007). About the septic group, the II-stage group had significant better post-operation KSS function scores, Society Function, physical component summary, WOMAC functional score and WOMAC score than I-stage group (t = 2.160-3.268, P = 0.004-0.042). The 1-year, 2-year, 6-year, 17-year survival rate were 83.6%, 78.7%, 62.1%, 44.5%. CONCLUSIONS: Revision total knee arthroplasty is an effective method for solving the failure of primary total knee arthroplasty. It can improve the pain and activity difficulty following the failure of primary total knee arthroplasty, and partially improve function along with quality of life. The results of non-infection group are better than infection group. There may be better results for II-stage revision total knee arthroplasty than I-stage revision. Both I-stage and II-stage revision total knee arthroplasty are effective.

Cadherin-11 involves in synovitis and increases the migratory and invasive capacity of fibroblast-like synoviocytes of osteoarthritis.

OBJECTIVE: To detect the expression of cadherin-11 and its correlation with synovitis in osteoarthritis (OA), to explore the mechanism of over expression of cadherin-11 and its role in migratory or invasive capacity of fibroblast-like synoviocytes (FLS). METHODS: Synovitis severity was recorded according to Krenn's scoring system in 25 osteoarthritis patients undergoing total knee arthroplasty. Cadherin-11 expression in OA synoviums and its correlation with synovitis score and systemic inflammation markers were explored. After induction with Interleukin-1 beta (IL-1ß) or tumor necrosis factor-alpha (TNF-α),cadherin-11 expression on OA FLS was assessed by qPCR and western blot,the capacity of migration and invasion of OA FLS was tested by transwell assay, and matrix metalloproteinase-2 production was assessed with ELISA as cadherin-11 expression was up regulated after infection with cadherin-11 cDNA-containing lentivirus, also when cadherin-11 expression was knocked down after infection with cadherin 11 shRNA containing lentivirus. RESULTS: Cadherin-11 expression in OA synovium showed significant differences among different grades of synovitis. Cadherin-11 in the lining layer was positively correlated with hyperplasia of the lining layer, density of the resident cells, inflammatory infiltrate, total synovitis score and D-dimer. Cadherin-11 in the sublining layer was positively correlated with the density of the resident cells, inflammatory infiltrate, total synovitis score and erythrocyte sedimentation rate. IL-1ß or TNF-α could up-regulate cadherin-11 expression on OA FLS at transcriptional and protein level. Over expression of cadherin-11 increased migratory or invasive capacity of OA FLS, while cadherin-11 knock down reduced migratory or invasive capacity and MMP-2 production in OA FLS. CONCLUSION: The over expression of cadherin-11 in osteoarthritis is positively correlated with synovitis severity, and can be driven by proinflammatory cytokines on OA FLS; cadherin-11 increases migratory or invasive capacity and MMP-2 production of fibroblast-like synoviocytes of osteoarthritis.

[Etanercept inhibits synovial inflammation and reduces the expression of adhesion related molecules in synovial tissues of patients with rheumatoid arthritis].

OBJECTIVE: To observe the changes of synovial inflammation score and expression of related molecular markers in patients with rheumatoid arthritis treated with tumor necrosis factor (TNF) antagonist etanercept. METHODS: Sixteen patients with rheumatoid arthritis received synovectomy in the knee under arthroscopy, of which 8 patients had been treated with etanercept before surgery (etanercept group) and the other 8 patients were given no etanercept or other biologics (non-biological agent group). The synovial tissues obtained from surgery were subjected to HE staining and immunohistochemical staining respectively, to assess Rooney's inflammation score and detect the expressions of proliferating cell nuclear antigen (PCNA), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and cadherin-11. RESULTS: Rooney's score in etanercept group was significantly lower than that in non-biological agent group. The expressions of PCNA and cadherin-11 in synovial lining and sublining layers significantly decreased in etanercept group. Expressions of VCAM-1 and ICAM-1 had no significant difference in either synovial lining or sublining layer between the two groups. Clinical inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count (PLT) and disease activity score in 28 joints (DAS28) had no statistical correlation with Rooney's inflammation score. CONCLUSION: Etanercept could effectively inhibit proliferation of synoviocytes and infiltration of lymphocytes in synovium of rheumatoid arthritis, and decrease the expressions of proliferation-and adhesion-related molecular markers, which histologically alleviated the synovial inflammation of rheumatoid arthritis. Clinical inflammatory markers might not fully reflect histological changes in the local synovial tissue.

Osmolarity influences chondrocyte repair after injury in human articular cartilage.

BACKGROUND: The purpose was to determine the influence of irrigation solution osmolarity on articular chondrocytes survival and metabolic state following mechanical injury. METHODS: Osteochondral explants were harvested from patients undergoing total knee arthroplasty for osteoarthritis and then cut through their full thickness to establish mechanical injury models. Cartilage explants were incubated in irrigation solutions (saline and balanced salt) with different osmolarities (180, 280, 380, 580 mOsm/L) for 2 h. The percentage of cell death (100 × number of dead cells/number of dead and live cells) was quantified with the laser confocal microscopy. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to detect apoptosis index of injured cartilage. The contents of proteoglycan elution were determined by spectrophotometer at 530 nm, and HIF-1α and type II collagen mRNA yields were quantified with real-time PCR. RESULTS: In situ dead chondrocytes were mainly localized to the superficial tangential region of injured cartilage edge after mechanical injury. The percentage of cell death was decreased, and proteoglycan elution was gradually reduced with the increasing of osmolarity. The apoptosis indices of TUNEL assay in different osmolarities had no significant difference (P = 0.158). HIF-1α and type II collagen mRNA yields were the least for chondrocytes exposed to 180 mOsm/L medium and were the greatest for chondrocytes exposed to 380 mOsm/L medium. Compared with the saline group, the cell death of superficial zone was significantly decreased (P = 0.001) and contents of proteoglycan elution were also significantly decreased (P = 0.045) in the balanced salt. HIF-1α (P = 0.017) and type II collagen (P = 0.034) mRNA yields in the chondrocytes exposed to the balanced salt were significantly more than the saline group. CONCLUSION: The osmolarity of irrigation solutions plays an important role in the survival and metabolic state of chondrocytes following mechanical injury, and the chondrocyte death is not caused by apoptosis. Increasing osmolarity of irrigation solutions may be chondroprotective with decreasing the chondrocyte death, reducing inhibition of metabolism and proteoglycan elution, ultimately preventing cartilage degeneration and promoting integrative repair.

[Expression of cadherin-11 in rheumatoid arthritis synovium and its correlation with inflammation].

OBJECTIVE: To explore the pattern of cadherin-11 expression and its relationship with synovial inflammation in rheumatoid arthritis (RA), and study the regulatory effects of cytokines on cadherin-11 expression on RA fibroblast-like synoviocytes (RAFLS). METHODS: Synovium samples were obtained from 28 RA patients who were undergoing total knee replacement. After HE staining, synovitis score was determined according to Rooney's inflammation score system. The expression of cadherin-11 in RA synovium was semi-quantified by immunohistochemical staining, and its correlations with Rooney's inflammation score and systematic inflammatory markers were analyzed statistically. After induction with transforming growth factor ß (TGF-ß) or interleukin 17 (IL-17) at a series of concentrations, the expression of cadherin-11 on RAFLS was assessed by real time guantitative-PCR and Western blotting. RESULTS: There was no significant difference in cadherin-11 expression in RA synovium among different levels of C-reactive protein. Cadherin-11 in the lining and sublining layers were positively correlated with D-dimer, synovial lining layer hyperplasia, proliferating blood vessels, perivascular infiltration of lymphocytes, focal aggregation of lymphocytes and diffuse infiltration of lymphocytes; cadherin-11 in the lining layer was negatively correlated with interstitial fibrosis. TGF-ß or IL-17 stimulation could up-regulate cadherin-11 expression on RAFLS at mRNA and protein levels. CONCLUSION: The over-expression of cadherin-11 in RA was correlated with synovial lining layer hyperplasia, proliferating blood vessels and infiltration of lymphocytes. Cadherin-11 expression on RAFLS could be induced by TGF-ß and IL-17 induction.

Working conditions of bipolar radiofrequency on human articular cartilage repair following thermal injury during arthroscopy.

BACKGROUND: The thermal injury during bipolar radiofrequercy results in chondrocyte death that limits cartilage repair. The purpose was to determine the effects of various factors of bipolar radiofrequency on human articular cartilage after thermal injury, offering suitable working conditions for bipolar radiofrequency during arthroscopy. METHODS: Osteochondral explants from 28 patients undergoing total knee arthroplasty (TKA) in Department of Orthopaedic, Peking University Reople's Hospital from October 2013 to May 2014, were harvested and treated using bipolar radiofrequency in a light contact mode under the following conditions: various power setting of levels 2, 4 and 6; different durations of 2 seconds, 5 seconds and 10 seconds; irrigation with fluids of different temperatures of 4°C, 22°C, and 37°C; two different bipolar radiofrequency probes ArthroCare TriStar 50 and Paragon T2. The percentage of cell death and depth of cell death were quantified with laser confocal microscopy. The content of proteoglycan elution at different temperatures was determined by spectrophotometer at 530 nm. RESULTS: Chondrocyte mortality during the treatment time of 2 seconds and power setting of level 2 was significantly lower than that with long duration or in higher level groups (time: P = 0.001; power: P = 0.001). The percentage of cell death after thermal injury was gradually reduced by increasing the temperature of the irrigation solutions (P = 0.003), the depth of dead chondrocytes in the 37°C solution group was significantly less than those in the 4°C and 22°C groups (P = 0.001). The proteoglycan elution was also gradually reduced by increasing the temperature (P = 0.004). Compared with the ArthroCare TriStar 50 group, the percentage of cell death in the Paragon T2 group was significantly decreased (P = 0.046). CONCLUSIONS: Thermal chondroplasty with bipolar radiofrequency resulted in defined margins of chondrocyte death under controlled conditions. The least cartilage damage during thermal chondroplasty could be achieved with lower power, shorter duration, suitable temperature of irrigation solutions and chondroprotective probes. The recommendations for the use of bipolar radiofrequency to minimize cartilage damage could be achieved with a power setting of level 2, treatment duration of 2 seconds, suitable fluid temperature (closer to body temperature of 37°C) and chondroprotective Paragon T2 probes.

Genistein inhibit cytokines or growth factor-induced proliferation and transformation phenotype in fibroblast-like synoviocytes of rheumatoid arthritis.

The purpose of this research is to study the effect of genistein on cytokines or growth factor-induced proliferation and transformation phenotype of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). RA-FLS were primarily cultured. With respective stimulation of IL-1ß, TNF-α, and EGF, genistein was applied to elucidate its effect on synoviocytes' growth number, cell proliferation assay, cell cycle using cell counts, (3)H-TdR incorporation and flow cytometry, the colony numbers under anchorage-independent condition, and the expression of MMP-2 and MMP-9 in synovial fibroblasts. EGF, IL-1ß, and TNF-α increased (3)H incorporation in RA-FLS, respectively. EGF augmented clone numbers of RA-FLS under anchorage-independent condition and not IL-1ß and TNF-α. Genistein had an inhibitory role on cell number and (3)H-TdR incorporation of RA-FLS stimulated with IL-1ß, TNF-α and EGF; genistein arrested the cell cycle at G(1) restriction point; genistein decreased colony numbers under anchorage-independent condition stimulated by EGF in serum condition. IL-1ß or TNF-α increased expression of MMP-9 and MMP-2 in rheumatoid synoviocytes; EGF stimulated expression of MMP-9 but not of MMP-2; genistein suppressed production of MMP-9 more than MMP-2 induced by IL-1ß or TNF-α; rMMP-9, rMMP-2, or their inhibitors had no effect on the (3)H-TdR incorporation of synovial cells. Erk1/2 inhibitor (PD098 059) had obvious inhibitory effect on the (3)H incorporation induced by TNF-α or IL-1ß; inhibitors of JNK (SP600 125) had no significant effect on the (3)H incorporation. While pretreatment with PD098059 had no marked inhibitory effect on MMP-9 expression induced by TNF-α or IL-1ß, SP600125 decreased significantly the MMP-9 expression induced by TNF-α or IL-1ß. Neither PD098059 nor SP600 125 could inhibit the MMP-2 expression induced by TNF-α or IL-1ß. Genistein inhibited IL-1ß, TNF-α or EGF-induced proliferation and MMP-9 expression in fibroblast-like synoviocytes of rheumatoid arthritis; the proliferation of RA-FLS was mediated by Erk1/2 but not JNK activation, while JNK activation was involved in the signal transduction pathway leading to MMP-9 expression in rheumatoid synoviocytes.

[Comparison of the status of STAT4 tyrosine phosphorylation in peripheral T-lymphocytes induced by IL-12 in rheumatoid arthritis and osteoarthritis].

OBJECTIVE: To compare the levels of STAT4 tyrosine phosphorylation in peripheral T-lymphocytes induced by IL-12 in rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: From May 2007 to August 2009, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients [RA group, all the cases were female, the age was from 28 to 55 years with an average of (45.0 +/- 13.0) years] and OA patients [OA group, all the cases also were female; the age was from 55 to 75 years with an average of (67.0 +/- 9.6) years]. The purity of T-lymphocytes from PBMCs was accredited by flow cytometry. The IL-12 of 50 ng/ml added in T-lymphocytes, the levels of STAT4 tyrosine phosphorylation were detected by western blot after different time intervals (0, 10, 30, 60 min). RESULTS: The purity of T-lymphocytes were above 91% through diremption and depuration for peripheral blood monouclear cells. The levels of STAT4 tyrosine phosphorylation in T-lymphocytes from RA induced by IL-12 were higher than that from OA in the different times (10, 30, 60 min); after 30 min, its levels from RA and OA achieved to crest value. CONCLUSION: STAT4 in peripheral T-lymphocytes of rheumatoid arthritis was more easily to be activated than osteoarthritis.

Discoidin domain receptor 2 is associated with the increased expression of matrix metalloproteinase-13 in synovial fibroblasts of rheumatoid arthritis.

Regulation of matrix metalloproteinase-13 (MMP-13) by collagen matrix in the synovial fibroblasts of rheumatoid arthritis (RA) is critical event in the progressive joint destruction. Our previous study indicated that a collagen receptor, discoidin receptor 2 (DDR2), was highly expressed in the synovial fibroblasts of RA. However, the functional role of DDR2 in the regulation of MMP-13 production in synovial fibroblasts has not been elucidated. In this study, we initially demonstrated that the DDR2 and MMP-13 proteins are both highly expressed in the synovial lining layer of RA. MMP-13 mRNA and protein in synovial fibroblasts of RA were preferentially induced by collagen type II compared with MMP-1. Furthermore, stable overexpression of wild type DDR2 in murine synoviocytes dramatically augments the production of MMP-13. The activation of DDR2 also mediates the up-regulation of MMP-13 promoter activity in 293T cells. Inhibitor specific for extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) cascade was shown to decrease MMP-13 level induced by collagen II in RA synovial fibroblasts and DDR2-induced MMP-13 promoter activity. Runx2 and activator protein-1 (AP-1) binding sites in MMP-13 promoter region are required for DDR2-induced transcription. The data in this study suggest that DDR2-mediated MMP-13 induction by collagen matrix in synovial fibroblasts of RA contributed to articular cartilage destruction.

Bony landmarks and rotational alignment in total knee arthroplasty for Chinese osteoarthritic knees with varus or valgus deformities.

The purpose of this study was to investigate the rotational mismatch of total knee arthroplasty when taking the medial one third of the tibial tuberosity as a rotational landmark in Chinese osteoarthritic knees. Computed tomographic images of 49 osteoarthritic knees (42 with varus and 7 with valgus deformities) and 10 healthy knees were analyzed. The angle (alpha) between the 2 baselines for the anteroposterior axis of the femoral and tibial components was measured. The mean value of alpha in healthy knees was +6.45 degrees, which increased significantly to +11.53 degrees in varus knees (P = .002) and +12.17 degrees in valgus knees (P = .04). It showed that there is a tendency for the tibial component to be externally rotated when the medial one third of the tibial tuberosity is defined as a rotational landmark. This finding is particularly prominent in Chinese osteoarthritic knees with varus or valgus deformities.

Subcellular distribution of the insulin-like growth factor (IGF) binding proteins (IGFBPs) 2 and 3 in articular chondrocytes.

The insulin-like growth factor (IGF) is a major anabolic regulator in articular cartilage. The IGF-binding proteins (IGFBPs) are increased during osteoarthritis (OA), but the function of the later proteins remains unknown. In general, the IGFBPs are pluripotential effectors capable of IGF regulation and of acting on their own to control key cell functions, including survival and proliferation. The independent functions are often associated with their cell location, and therefore this study explores the distribution of IGFBP-2 and IGFBP-3 in articular chondrocytes. Immunohistochemistry was used to localize IGFBP-2 in normal human articular cartilage. Bovine chondrocytes were used for subcellular fractionation (hypotonic cell lysis) under nonreducing conditions and nuclear purification (centrifugation on sucrose cushions). Cell fraction markers and IGFBPs were assayed in the subcellular fractions by Western immunoblot. The IHC results showed association of IGFBP-2 with chondrocytes, but not with the nuclei. Subcellular fractionation of isolated chondrocytes yielded intact nuclei as assessed at the light microscopic level; the nuclear marker histone H1 was exclusively associated with this fraction. More than 90% of the cytoplasmic marker GAPDH and all the detectable IGFBP-2 were in the cytoplasmic fraction. Immunoreactive IGFBP-3 was found in the cytoplasmic and peri-nuclear/nuclear fractions. Chondrocytes contain intracellular IGFBP-2 and IGFBP-3 but only IGFBP-3 is associated with nuclei. This suggests the hypothesis that the actions of these IGFBPs in articular cartilage extend beyond the classic modulation of IGF receptor action.