No difference in clinical outcome, pain, and range of motion between fixed and mobile bearing Attune total knee arthroplasty: a prospective single-center trial.

BACKGROUND: Despite numerous scientific investigations, the tribological advantages of mobile bearing inserts have not been sustainably confirmed or refuted for modern knee prostheses in clinical studies. The purpose of this study was to compare fixed and mobile bearing inserts in order to draw conclusions regarding clinical benefits. METHODS: The present prospective single center cohort study of 2 non-randomized stratified groups consisted of 67 patients. All included patients received cemented total knee arthroplasty (Attune®) due to osteoarthritis. 34 patients were treated with a mobile and 33 patients with a fixed insert. The WOMAC score and the Visual Analogue Scale was used for the subjective assessment of success, while the Knee-Society-Score was used considering the Range of Motion for the objective assessment. The subjective and the clinical scores showed improvements for both compared groups postoperatively at 2 years of minimum follow-up. RESULTS: The overall postoperative results of the WOMAC score, the Knee-Society-Score and the Visual Analogue Scale presented no statistically difference between the compared groups (p > 0,05). The postoperative ROM showed a superior improvement of 13.2° ± 18.4° in the mobile-bearing group versus 4.9° ± 18.4° (p = 0.017) in the fixed-bearing group. The flexion of the knee joint was 114° ± 10.1° for the mobile-bearings and 109.2° ± 7.2° for fixed bearings (p = 0.012). CONCLUSION: According to the findings, both inserts showed overall promising postoperative results, in terms of objective as well as subjective parameters, without clinically relevant significant differences, except for ROM, which was superior in the mobile bearing group. The present clinical trial has been registered at the ISRCTN registry with the reverence number ISRCTN15117998 on 04/04/2022.

Long-term outcomes of surgery using the Ligament Advanced Reinforcement System as treatment for anterior cruciate ligament tears.

AIMS: The aim of this prospective study was to assess the long-term clinical, radiological, functional, and quality of life (QoL)-related outcome of patients treated with the synthetic Ligament Advanced Reinforcement System (LARS) device for anterior cruciate ligament (ACL) rupture. METHODS: A total of 41 patients who underwent ACL reconstruction with the LARS device (mean age 39.8 years (SD 12.1 ); 32% females (n = 13)) were prospectively included between August 2001 and March 2005. MRI scans and radiographs were performed at a median follow-up of 2.0 years (interquartile range (IQR) 1.3 to 3.0; n = 40) and 12.8 years (IQR 12.1 to 13.8; n = 22). Functional and QoL-related outcome was assessed in 29 patients at a median follow-up of 12.8 years (IQR 12.0 to 14.0) and clinically reconfirmed at latest median follow-up of 16.5 years (IQR 15.5 to 17.9). International Knee Documentation Committee (IKDC) and Tegner scores were obtained pre- and postoperatively, and Lysholm score postoperatively only. At latest follow-up, range of motion, knee stability tests, 36-Item Short Form Health Survey (SF-36), and IKDC scores were ascertained. Complications and reoperations during follow-up were documented. RESULTS: Cumulative complication rate was 66% (n = 27), with 11 developing within one year from surgery and 16 after one year (including five patients with both early and late complications). Ten graft failures (24%) and eight cases of reactive synovitis were observed (20%). All 11 patients with early complications and ten with late complications underwent reoperation (including five with another surgical procedure for early complications), amounting to a cumulative reoperation rate of 51% (n = 21). Revision ACL reconstruction was performed in one patient (2.4%). Median IKDC at latest follow-up was 89.7 (IQR 78.2 to 93.1), being significantly worse in the event of previous complications. Lachman test was positive in 56% (n = 15) of reconstructed knees. All norm-based SF-36 items were at or above median at latest follow-up, and did not differ depending on development of complications. CONCLUSION: Despite good functional and QoL-related results in the long term, the cumulative complication rate of 66%, including graft failures and reactive synovitis, has to be viewed with great concern. Cite this article: Bone Joint J 2022;104-B(2):242-248.

Patellar Tendon Length is Associated with Lower Extremity Length but Not Gender.

BACKGROUND: The aim of this study was to evaluate the patellar tendon length (PTL) with focus on gender differences and possible correlations with the total leg length (TLL) and the long bones of the lower extremity. MATERIALS AND METHODS: The sample involved 50 paired lower extremities from human adult cadavers. The TLL was measured between the medial malleolus and the apex of the greater trochanter. The femoral length (FL) was evaluated as the interval between the latter and the distal margin of the lateral epicondyle of the femur and the tibial length (TL) from the distal apex of the medial malleolus to the proximal border of the medial condyle of the tibia. The PTL was measured from the apex of the patella to its proximal insertion point at the tibial tuberosity. RESULTS: The PTL was at a mean length of 4.29 ± 0.49 cm (right side) and 4.20 ± 0.55 cm (left side) in females and 4.42 ± 0.53 cm (right) and 4.32 ± 0.55 cm (left) in males. There were no differences regarding gender (p = .412). The left PTL was significantly shorter in both sexes (p = .022). The PTL correlated positively with FL, TL, and TLL in both sexes and sides. CONCLUSION: PTL correlates significantly positively with size without gender differences.

Similar revision rates in clinical studies and arthroplasty registers and no bias for developer publications in unicompartmental knee arthroplasty.

PURPOSE: Our aim was to assess the outcome with respect to cumulative revision rates of unicompartmental knee arthroplasty (UKA) by comparing published literature and arthroplasty registry data. Our hypothesis was that there is a superior outcome of UKA described in dependent clinical studies compared to independent studies or arthroplasty registers. METHODS: A systematic review of all clinical studies on UKA in the past decade was conducted with the main endpoint revision rate. Revision rate was calculated as "revision per 100 component years (CY)". The respective data were analysed with regard to a potential difference of the percentage of performed revision surgeries as described in dependent and independent clinical studies. Clinical data were further compared to arthroplasty registers in a systematic search algorithm. RESULTS: In total, 48 study cohorts fulfilled our inclusion criteria and revealed 1.11 revisions per 100 CY. This corresponds to a revision rate of 11.1% after 10 years. No deviations with regard to revision rates for UKA among dependent and independent clinical literature were detected. Data from four arthroplasty registers showed lower survival rates after 10 years compared to published literature without being significant. CONCLUSIONS: The outcomes of UKA in dependent and independent clinical studies do not differ significantly and are in line with arthroplasty register datasets. We cannot confirm biased results and the authors recommend the use of UKAs in properly selected patients by experts in their field.

Greater activity, better range of motion and higher quality of life following unicompartmental knee arthroplasty: a comparative case-control study.

PURPOSE: The purpose of this study was to provide a matched cohort comparison of clinical and functional outcome scores, range of motion and quality of life following unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA). The hypothesis was that patients receiving UKA report better results than comparable patients who receive conventional TKA. METHODS: Clinical and functional results of 35 patients with medial end-stage osteoarthritis who had received a fixed-bearing UKA were compared with the results of 35 matched patients who had received a TKA from the same manufacturer by the same surgeon. Outcome scores were measured before surgery and at final follow-up using Tegner Activity Scale (TAS), range of motion (ROM) and Short Form 36 Health Survey (SF-36). The Knee Society Score (KSS) was assessed at final follow-up. The mean observation period was 2.3 years in both groups. RESULTS: The preoperative knee scores had no statistically significant differences between the two groups. Postoperatively, however, UKAs performed significantly better regarding TAS and ROM (4 vs. 3 and 118.4 vs. 103.7, respectively). The results of the SF-36 showed significantly better results for the UKA group in the mental component summary score and in the subscale of social function. CONCLUSIONS: The present study suggests that UKA is associated with higher activity level, higher quality of life, and greater ROM when compared with TKA on comparable patients. Prolonged clinical follow-up in a larger patient cohort with a randomised-controlled study design would be beneficial to confirm these findings. LEVEL OF EVIDENCE: III.

Septic Revision Total Knee Arthroplasty: Treatment of Metaphyseal Bone Defects Using Metaphyseal Sleeves.

BACKGROUND: Bone loss is a severe problem in septic revision total knee arthroplasty (RTKA). The use of porous coated metaphyseal sleeves is a promising treatment option for metaphyseal bone defects. The currently published midterm results remain limited and no study has been focused exclusively on septic cases. Our aim was to determine the implant survivorship (with special focus on osseointegration) and the clinical and radiological midterm outcome of metaphyseal sleeve fixation in septic RTKA surgery (minimum follow-up of 2 years). METHODS: We performed a clinical and radiographic examination of 56 patients with a history of prosthetic joint infection who underwent 2-stage RTKA with the use of porous coated metaphyseal sleeves. These examinations included evaluation of the American Knee Society Score, the Western Ontario and McMaster Universities Osteoarthritis Index, the Short Form (SF-36) Health survey as well as radiographic measurement to determine whether successful osseointegration had been achieved. RESULTS: Nine patients (16%) had to be re-revised at the time of follow-up (mean, 5.3 years; range, 2-11.2), all due to reinfection. We did not encounter any cases of aseptic loosening. The mean range of motion (92°, SD ± 21°), subjective satisfaction score (7, SD ± 2), American Knee Society Score (76, SD ± 19), Western Ontario and McMaster Universities Osteoarthritis Index (70, SD ± 20), SF-36 mental component summary (55, SD ± 14), and SF-36 physical component summary (35, SD ± 9) have shown satisfying results. CONCLUSION: Metaphyseal sleeves have shown very promising midterm results regarding clinical scores, osseointegration, and aseptic loosening. Our results are the first analyzing exclusively septic indications and indicate that they are a reliable fixation option in all bone defect types in septic RTKA patients.

Impact of a new cryotherapy device on early rehabilitation after primary total knee arthroplasty (TKA): a prospective randomised controlled trial.

BACKGROUND: The aim of this prospective, randomised and single blinded study was to evaluate the efficiency and safety of a new cryotherapy device in patients undergoing unilateral, primary total knee arthroplasty (TKA). Our hypothesis was that patients administered to the new cryotherapy device would perform better than patients receiving a conventional standard cold therapy regimen. METHODS: Ninety-seven patients were randomised into two groups receiving either the cTreatment® (new cryotherapy device) or the standard cold therapy protocol (including cold pack application for six days after the surgical intervention). We evaluated the following endpoints consisting of range of motion (ROM), pain intensity, and knee girth on admission day and the second, fourth, and sixth post-operative day (POD). RESULTS: A statistically significant benefit of the new cryotherapy device was detected regarding the ROM on the sixth POD with an average gain of 7 degrees (p = 0.021). Pain in the numeric rating scale (NRS) score in motion was significantly lower in the cTreatment® group on the second POD (p = 0.034). There were no statistically significant differences between groups regarding the NRS in rest, patient controlled analgesia (PCA) consumption, and girth measurements. No adverse effects were observed in both study groups. CONCLUSION: The new computer-controlled cooling therapy device provides benefits in terms of early post-operative remobilisation with respect to ROM and pain, which might be attributed to a reduced inflammatory response, as well as reduced secretion and bleeding. The cTreatment® system appears to be a safe and efficient procedure.

A Novel Surgical Technique for Fixation of Recurrent Acromioclavicular Dislocations: AC Dog Bone Technique in Combination with Autogenous Semitendinosus Tendon Graft.

Various surgical techniques have been described for the fixation of acromioclavicular (AC) dislocations. However, recurrent dislocation is one of the main complications associated with the majority of these techniques. We report a case of postoperative AC joint redislocation. In order to overcome recurrent dislocation after revision surgery, a reconstruction of the conoid and trapezoid ligament with the use of a free tendon graft in combination with a FiberTape was provided within a novel surgical technique. After 12 months, the patient was very satisfied with the functional outcome. The patient achieved excellent results in the Constant (98 points), SPADI (0 points), and QuickDASH score (0 points). The described technique results in an anatomic reconstruction of the AC joint. The nonrigid nature of the intervention seems to restore the normal arthrokinematics by reconstructing the coracoclavicular ligaments with an autograft which is then protected by the AC Dog Bone artificial ligaments during the healing period. The arthroscopic approach to the AC joint with minimal exposure reduces the risks and complications of the intervention. This is the first case in literature that utilizes the artificial dog bone ligament securing the autograft in an anatomic AC reconstruction.

Chondrocyte cultures from human proximal interphalangeal finger joints.

Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described. Chondrocyte culture has been essential to understand cartilage degeneration, which is a hallmark of OA. We investigated the feasibility of human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints. Hyaline cartilage of the PIP and knee joints was obtained from human cadavers. Chondrocytes harvested up to 236 h after death of the donors were viable and expressed chondrocyte-specific genes. Gene expression comparing chondrocytes from PIP and knee joints using Affymetrix GeneChip arrays resulted in a unique PIP-specific gene expression pattern. Genes involved in developmental processes including the WNT pathway were differentially expressed between the joints. These findings suggest that our knowledge on chondrocyte biology derived mainly from knee and hip joints may not apply to chondrocytes of the PIP joints and some of the distinctive features of HOA may be caused by the specific properties of PIP chondrocytes. Chondrocyte culture of PIP cartilage is a novel tool to study cartilage degeneration in HOA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1569-1575, 2016.

Effect of Laminin-A4 inhibition on cluster formation of human osteoarthritic chondrocytes.

Formation of chondrocyte clusters is not only a morphological sign of osteoarthritis but it is also observed in cell culture. Active locomotion of chondrocytes is controlled by integrins in vitro. Integrins bind to Laminin-A4 (LAMA4), a protein that is highly expressed in vivo in clusters of hypertrophic chondrocytes. We tested if LAMA4 is relevant for cluster formation. Human chondrocytes were cultured in a 2D matrigel model and treated with different concentrations of a monoclonal inhibitory anti-LAMA4-antibody. Migration and cluster formation was analysed using live cell imaging technique. Full genome gene expression analysis was performed to assess the effect of LAMA4 inhibition. The data set were screened for genes relevant to cell motility. F-actin staining was performed to document cytoskeletal changes. Anti-LAMA4 treatment significantly reduced the rate of cluster formation in human chondrocytes. Cells changed their surface morphology and exhibited fewer protrusions. Expression of genes associated with cellular motility and migration was affected by anti-LAMA4 treatment. LAMA4-integrin signalling affects chondrocyte morphology and gene expression in vitro, thereby contributing to cluster formation in human osteoarthritic chondrocytes.

Epigenetic differences in human cartilage between mild and severe OA.

The development of osteoarthritis (OA) depends on genetic and environmental factors, which influence the biology of the chondrocyte via epigenetic regulation. Changes within the epigenome might lead the way to discovery of new pathogenetic pathways. We performed a genome-wide methylation screening to identify potential differences between paired mild and severe osteoarthritic human cartilage. Sixteen female patients suffering from OA underwent total knee joint replacement. Cartilage specimens collected from corresponding macroscopically undamaged and from damaged areas were processed for DNA extraction and histology to evaluate the histological grading of the disease. Paired specimens were analysed for the methylation status of the whole genome using human promoter microarrays (Agilent, Santa Clara, CA). Selected target genes were then validated via methylation-specific qPCR. One thousand two hundred and fourteen genetic targets were identified differentially methylated between mild and severe OA. One thousand and seventy of these targets were found hypermethylated and 144 hypomethylated. The descriptive analysis of these genes by Gene Ontology (GO), KEGG pathway and protein domain analyses points to pathways of development and differentiation. We identified a list of genes which are differently methylated in mild and severe OA cartilage. Within the pathways of growth and development new therapeutic targets might arise by improving our understanding of pathogenetic mechanisms in OA.

Quality of life after volar locked plating: a 10-year follow-up study of patients with intra-articular distal radius fractures.

BACKGROUND: This study aimed to present functional results and patient's health related quality of life (HRQOL) data ten years after volar locked plate fixation (VPF) of unstable intra-articular distal radial fractures (DRF). METHODS: Thirty-nine patients with a mean age of sixty-one years were operatively treated with VPF after intra-articular distal radial fractures. They were evaluated two, six, and ten years postoperatively according to the Gartland and Werley score. For subjective evaluation the Short Form 36 (SF-36) and the Disability of Arm, Shoulder and Hand (DASH) questionnaires were adopted. RESULTS: Overall, wrist function did not differ significantly two, six and ten years after the operation. Over 90% patients achieved "good" or "excellent" results ten years after surgery according to the Gartland and Werley score. Ten years postoperatively the results of the SF 36 did not differ significantly from the two- and six-year follow-up. Overall findings from the SF-36 did not differ significantly from the data of Austrian and American norm populations. Only in the subscale of mental health (MH) the ten-year follow-up did show significantly poorer results (p = 0.045) compared to the Austrian norm population. The median DASH scores did not show significant differences during the ten-year follow-up period. CONCLUSION: The ten-year results of this single-center study suggest that operative treatment of intra-articular DRF with volar locked plates is a useful and satisfactory therapy option, both in terms of function and HRQOL.

Gender-specific outcome after implantation of low-contact-stress mobile-bearing total knee arthroplasty with a minimum follow-up of ten years.

PURPOSE: The study aim was an analysis of gender-specific outcome differences after implantation of the low-contact-stress (LCS) mobile-bearing total knee arthroplasty (TKA) with a minimum follow-up of ten years. METHODS: We retrospectively analysed 138 prostheses in 108 patients (82 women and 26 men) using our hospital database and a minimum follow-up of ten years (mean 14, range 11-23). Data was extracted with respect to quality of life, clinical outcome parameters [range of motion (ROM), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analogue scale (VAS), Knee Society Score (KSS), and complications. RESULTS: At follow-up, we observed no statistically significant differences in all outcome parameters between female and male patients after LCS TKA, except for VAS score, which revealed no clinical relevance due to the low difference (1.53 vs 1.03, p = 0.043). CONCLUSIONS: Ten years after implantation of the LCS TKA, gender did not influence its beneficial outcome.

Noise measurement in total knee arthroplasty.

Few studies have been performed to analyze noise levels produced by various surgical instruments in the operating room (OR). The highest levels of noise that have been described were due to instruments used for total knee arthroplasty (TKA). These high levels of noise might be a potential health hazard for patients and medical staff. Therefore, we aimed to measure noise levels of current instruments that are widely used worldwide. During a conventional primary TKA the levels of noise in the OR were measured using a Class 1 integrating-averaging sound level meter. The highest A-weighted equivalent level was produced when using a hammer during the implantation of the femoral and tibial components with 90.2 dBA. In total surgical instruments were used for about 10% of the total time of surgery. Noise exposure due to instrument use during TKA does not seem to be a potential health hazard for medical staff or patients.

Physician awareness of knee and hip pain in the context of coronary heart disease treatment.

BACKGROUND: The benefit of physical activity for the prevention and treatment of cardiovascular disease (CVD) has been well documented. The aim of the present study was to determine the level of awareness among general practitioners (GPs) of knee and hip problems in patients with CVD or CVD risk. DESIGN: Cross-sectional questionnaire survey. SETTING AND SUBJECTS: Thirty-five Austrian GPs and 1,118 patients were included. The GPs completed an extraction form about the presence or absence of documented evidence of problems related to the knee and/or hip joint within the patient medical data. Patients, in turn, were asked to complete a questionnaire that included the Oxford Knee/Hip Score and the cardiovascular risk-chart established by the European Society of Cardiology. RESULTS: In 748 patients' data from medical records and questionnaires were available. 40.9% of these patients suffered from serious knee pain and 32.1% from hip pain. However, in the medical records, in only 51.3% (knee) and 48.1% (hip) of these pain-patients the problems were documented. CONCLUSION: Joint disorders of the knee and hip problems are considerable barriers to effective physical activity and can therefore contribute to the development of CVD. Our data showed that GP awareness of such knee/hip disorders should be improved.

Prosthetic joint infection following total hip replacement: results of one-stage versus two-stage exchange.

PURPOSE: Prosthetic hip joint infection remains a challenging socio-economic problem. Curative treatment is usually a one- or two-stage revision surgery, but neither of these options has yet emerged as the treatment of choice. The aim of this study was to evaluate which of these methods produced superior outcomes. METHODS: A retrospective study was performed including 92 patients with deep infections after implantation of primary total hip arthroplasty (THA) who had undergone either one-stage or two-stage revision surgery at a single centre. Infections were classified according to McPherson and we evaluated the rate of persisting infection or reinfection after surgical intervention. RESULTS: The two-stage revision surgery revealed superior outcomes for the analysed infection categories compared to the one-stage procedure except for the least serious category of infections (i.e. McPherson Stage I/A/1, early postoperative infection, no systemic comorbidities, local status uncompromised). Eradication of prosthetic infection was achieved in 94.5 % (n = 52) within the group of two-stage exchange, and 56.8 % (n = 21) of patients treated with a one-stage procedure. Outcome of patients following a one-stage or a two-stage exchange was overall significantly different with p < 0.001. Further deviations between the described two procedures were noted in the subgroups following the classification described by McPherson. CONCLUSIONS: Our results indicate superiority of two-stage revision surgery in case of serious infections. The authors believe that decisions on the surgical approach for the treatment of deep prosthesis infections should be made on the basis of standardized staging systems.

Health-related quality of life after TAPP repair for the sportsmen's groin.

BACKGROUND: Sportsmen's groin (SG) is a clinical diagnosis of chronic, painful musculotendinous injury to the medial inguinal floor in the absence of a groin hernia. Long-term results for laparoscopic inguinal hernia repair, especially data on health-related quality of life (HRQOL), are scant and there are no available data whatsoever on HRQOL after SG. The main goal of this study was to compare postoperative QOL data in the long term after transabdominal preperitoneal hernioplasty (TAPP) in groin hernia and SG patients with QOL data of a normal population. METHODS: This study included all patients (n = 559) who underwent TAPP repair between 2000 and 2005. Forty seven patients (8.4 %) were operated on for SG. We sent out the Short Form 36 Health Survey (SF-36) questionnaire for QOL evaluation. QOL data were compared with data from an age- and sex-matched normal population. RESULTS: Ultimately, 383 completed questionnaires were available for evaluation (69 % response rate). The mean follow-up time was 94 ± 20 months. In the SG group there were statistically significant differences in three subscales of the SF-36 and the mental component summary measure, showing better results for the SG group compared to the sex- and age-matched normal group data. There were no statistically significant differences between groin hernia patients and the sex- and age-matched normal population. CONCLUSION: TAPP repair for SG as well as groin hernia results in good HRQOL in the long term. Results for SG patients are comparable with QOL data of a normal population or even better.

Application and surgical technique of total knee arthroplasties: a systematic comparative analysis using worldwide registers.

PURPOSE: The aim of this study was to compare total knee arthroplasty (TKA) procedures between different countries with regard to epidemiological data and surgical technique by reference to the worldwide arthroplasty registers. METHODS: A systematic search was carried out using the EFORT website to identify the relevant arthroplasty registers. We extracted data with respect to the number of implanted TKAs, patients' age distribution, procedure types, and revision rates. After identification of 28 national arthroplasty registers, 11 offered sufficient data regarding the above mentioned parameters and were therefore included in the final analysis. RESULTS: A large variation was found in the annual number of primary TKA implantations per inhabitant with a reported range from 30 to 199 per 100,000 (mean 106). The fixation method varied strongly between the different registers as well, e.g. 90 % of totally cemented TKAs in Sweden, England and Wales, Slovakia, and New Zealand versus 54 % cemented fixation in Australia. Another significant difference between included countries was observed with respect to the use of patellar resurfacing in TKA. Whilst the Danish knee arthroplasty register reports a percentage of 72 % using a patellar button in TKA the register from Norway reports only a minority of 2 %. CONCLUSIONS: The comparison of arthroplasty registers revealed large differences regarding the annual number of primary TKAs per inhabitant and primary TKA procedure types. These variations may be explained by several factors such as patient demographics (prevalence of osteoarthritis) and national conditions such as healthcare systems (insurance status), number or availability of performing surgeons, medical facilities and surgeon-dependent factors such as definition of indications, education, tradition and experience.

Sphingosine 1-phosphate counteracts the effects of interleukin-1ß in human chondrocytes.

OBJECTIVE: The lipid mediator sphingosine 1-phosphate (S1P) is found in the synovial fluid of osteoarthritis (OA) patients. S1P protects bovine cartilage by counteracting the effects of interleukin-1ß (IL-1ß). This study was undertaken to examine the interaction of S1P and IL-1ß in human OA chondrocytes. METHODS: Human cartilage was obtained from patients undergoing total knee joint replacement. Chondrocytes were cultured in monolayer and treated with IL-1ß and S1P. Expression of S1P receptor subtypes and genes involved in cartilage degradation was evaluated using real-time polymerase chain reaction, immunohistochemistry, and Western blotting. S1P signaling was evaluated using inhibitors of S1P receptors and small interfering RNA (siRNA) knockdown of the S1P2 receptor. Phosphorylation of MAP kinases and NF-κB in response to IL-1ß and S1P was detected by Western blotting. RESULTS: S1P2 was identified as the most prevalent S1P receptor subtype in human OA cartilage and chondrocytes in vitro. S1P reduced expression of inducible nitric oxide synthase (iNOS) in IL-1ß-treated chondrocytes. Reduction of ADAMTS-4 and matrix metalloproteinase 13 expression by S1P correlated with S1P2 expression. Pharmacologic inhibition of the S1P2 receptor, but not the S1P1 and S1P3 receptors, abrogated the inhibition of iNOS expression. Similar results were observed using siRNA knockdown. S1P signaling inhibited IL-1ß-induced phosphorylation of p38 MAPK. CONCLUSION: In human chondrocytes, S1P reduces the induction of catabolic genes in the presence of IL-1ß. Activation of the S1P2 receptor counteracts the detrimental phosphorylation of p38 MAPK by IL-1ß.