First insights into human acetabular labrum cell metabolism.

OBJECTIVE: Hip labrum pathology has only begun to emerge as a significant source of groin pain in the last decade since the development of hip arthroscopy. Few data are available on the anatomy, histology and function of this structure. Moreover, no metabolic data exist at cellular level. The aim of this study was to characterize extracellular matrix (ECM) genes and pro-inflammatory mediators expressed by these cells. METHODS: Isolated human acetabular labrum cells were cultured in alginate beads for 10 days and additionally stimulated with interleukin (IL)-1 for 24 h. Gene expression levels and secretion of different ECM genes, enzymes and cytokines were examined by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) to assess the metabolic characteristics of labrum cells. Articular chondrocytes and meniscus cells served as controls. RESULTS: Labrum cells expressed high levels of COL1A1 and low levels of COL2A1, aggrecan and SOX-9 compared to chondrocytes. However, COL2A1 was more expressed by labrum cells than by meniscus cells. The expression of matrix metalloproteinase (MMP)-1/-2/-9, ADAMTS-4 and IL-6 was significantly higher in labrum cells than in chondrocytes. IL-1 suppressed the ECM gene expression levels of labrum cells, but increased the expression levels and release of MMP-1/-3/-9/-13 and ADAMTS-4 and IL-6 by these cells. Remarkably, MMP-9 was only significantly upregulated in acetabular labrum cells. CONCLUSIONS: The findings in this study demonstrated that the acetabular labrum is populated with unique highly active fibrochondrocyte-like cells. These cells are capable of expressing and releasing pro-inflammatory enzymes and cytokines and react to a pro-inflammatory stimulus. In this way, they contribute obviously to disturbed tissue function in hip labrum pathology.

The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage.

PURPOSE: The purpose of this short-term pilot study was to determine the clinical and MRI outcome of a combination of microfracture with a cell-free polymer-based matrix for the treatment of cartilage defects in the knee. METHODS: The technique was used for treatment of symptomatic cartilage defects in the knee. Five patients were prospectively evaluated during 2 years with use of the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and the visual analog scale (VAS). MRI data were analyzed based on the original and modified MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scoring system at 6, 12 and 24 months of follow-up. RESULTS: A gradual clinical improvement was observed during the follow-up. Adverse reactions to the matrix were not observed. The scaffold was firmly fixed with the use of bioresorbable pins. Both MOCART scoring systems revealed no significant deterioration or improvement in the repair tissue during the follow-up period. However, the majority of the patients exhibited subchondral lamina and bone changes. The formation of an intralesional osteophyte was observed in one case. CONCLUSIONS: The key finding in this study was that this procedure is safe for the treatment of cartilage defects in the knee. The patients showed a gradual clinical improvement postoperatively. Sixty percent (3/5) of the defects were adequately (complete or hypertrophic) filled with repair tissue at 2 years of follow-up. LEVEL OF EVIDENCE: IV.

Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee.

PURPOSE: To evaluate short-term clinical and MRI outcome of the second generation characterized chondrocyte implantation (CCI) for the treatment of cartilage defects in the knee. METHODS: Thirty-two patients aged 15-51 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of different locations in the knee were treated with CCI using a synthetic collagen I/III membrane to cover the defect. Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) for pain. Serial magnetic resonance imaging (MRI) scans of 22 patients were scored using the original and modified Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system. RESULTS: The patients included in this study showed a significant gradual clinical improvement after CCI. The MRI findings of this pilot study were considered to be promising. No signs of deterioration were observed. A complete or hypertrophic filling was observed in 76.5% of the cases at 24 months of follow-up. No preventive effect of an avital membrane on the occurrence of hypertrophic repair tissue was observed on MRI. Three failures were observed among the 32 patients until now (9.4%). CONCLUSIONS: This investigation provided useful information on the efficacy of this treatment. The short-term clinical and MRI outcome are promising. Large-scale and long-term trials are mandatory to confirm the results and the reliability of this procedure. LEVEL OF EVIDENCE: IV.

Autologous matrix-induced chondrogenesis combined with platelet-rich plasma gel: technical description and a five pilot patients report.

PURPOSE: This pilot study was designed to describe the technical details and to present the preliminary outcome of autologous matrix-induced chondrogenesis (AMIC) combined with platelet-rich plasma gel, the so called AMIC plus technique, for the treatment of patellar cartilage defects in the knee. METHODS: The AMIC plus technique was used for the treatment of (osteo) chondral patellar lesions in the knee. The surgical technique is extensively described. Five patients were clinically prospectively evaluated during 2 years. MRI data were analysed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. RESULTS: A clinical improvement became apparent after 24 months of follow-up. Both MOCART scoring systems revealed no significant deterioration or improvement of the repair tissue between one and 2 years of follow-up. However, all cases showed subchondral lamina and bone changes. The formation of intralesional osteophytes was observed in 3 of the 5 patients during the 2 years of follow-up. CONCLUSIONS: AMIC plus is feasible for the treatment of symptomatic patellar cartilage defects and resulted in a clinical improvement in all patients. The favourable clinical outcome of the AMIC plus technique was not confirmed by the MRI findings. LEVEL OF EVIDENCE: IV.

MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair.

AIM: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. METHODS: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. RESULTS: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. DISCUSSION: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further validation of these scoring systems is mandatory. The promising short-term clinical outcome of the allogenic chondrocytes/alginate beads implantation was not confirmed by the short-term MRI findings.

Melanoma inhibitory activity, a biomarker related to chondrocyte anabolism, is reversibly suppressed by proinflammatory cytokines in rheumatoid arthritis.

OBJECTIVE: In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific molecule with similar regulation to collagen type II. As MIA is a small secreted protein, its value as cartilage biomarker in human inflammatory arthritis was assessed. METHODS: MIA tissue distribution was studied by quantitative PCR and immunohistochemistry. The regulation of MIA production was studied in vivo in rheumatoid arthritis (RA) (n = 37) and spondyloarthritis (SpA) (n = 30) synovial fluid (SF), and in vitro in alginate embedded human chondrocytes. Therapeutic modulation of serum MIA was evaluated during tumour necrosis factor (TNF)alpha and interleukin (IL)1 blockade in RA. RESULTS: MIA was primarily expressed by chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA despite similar levels of overall synovial inflammation. Further analysis indicated that these levels were inversely correlated with the degree of joint inflammation in RA, but not in SpA, and that the levels of TNFalpha and IL1beta were significantly increased in RA versus SpA. Accordingly, these proinflammatory cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This suppression was paralleled by suppression of cartilage anabolism as assessed by collagen type 2 and aggrecan mRNA. Treatment of patients with RA with TNF blockade or IL1 blockade induced an increase of serum MIA levels. CONCLUSION: The decreased levels of MIA in the inflamed RA joint and the coregulation of MIA and cartilage matrix molecules by proinflammatory cytokines indicate that joint inflammation in RA not only drives accelerated cartilage degradation but also suppresses cartilage anabolism. This inflammation-driven suppression is reversible in vivo.

Medial unicompartimental knee arthroplasty for osteonecrosis or osteoarthritis.

We report a prospective series of 33 unicompartmental knee arthroplasties (UKAs) operated for a spontaneous osteonecrosis of the knee (SPONK) compared with 35 UKAs operated for osteoarthritis (OA). The mean follow-up was 5 years. Preoperative functional score in the SPONK group was significantly lower than that in the OA group. The results were comparable in terms of pain, knee score and function. At the last follow-up, the survival rate was 92.8% for the SPONK group and 95.4% for the OA group. We found a higher rate of radiolucencies in the SPONK group, however, without any clinical symptoms. The UKA is a good option in the treatment of SPONK.

Differential proteome analysis of normal and osteoarthritic chondrocytes reveals distortion of vimentin network in osteoarthritis.

OBJECTIVE: We conducted a proteome analysis of human articular chondrocytes, in order to identify proteins differentially expressed in chondrocytes during the progression of osteoarthritis (OA) and to characterize the phosphorylation status of these proteins. METHODS: The proteins of 20 samples of human chondrocytes obtained from the cartilage of human knees (six from healthy cartilage (NoNo), seven from visually intact zones (NoOA) and seven from visually damaged zones (OAOA) of OA cartilage from the same knee joint) were sequentially extracted and subjected to two-dimensional gel electrophoresis (2-DE). Protein expression patterns were subjected to statistical analysis and protein spots of interest were identified by electrospray ionization tandem mass spectrometry. RESULTS: We identified several protein spots, showing a differential expression between the sample groups. Cleaved vimentin was upregulated in OAOA samples, this was confirmed by 1-DE and Western blot. The possible impact of vimentin cleavage on the chondrocyte's cytoskeleton was illustrated by confocal microscopy analysis, which revealed a distorted vimentin organization in OA chondrocytes. In contrast, F-actin staining did not reveal differences. CONCLUSION: All together, this study revealed substantial alterations in the vimentin cytoskeleton in OA-affected human articular chondrocytes.

[A comparison of all-polyethylene and metal-backed tibial components in total knee arthroplasty]. / Comparaison entre embase tibiale métallique et plateau tout polyéthylène dans la prothèse totale de genou.

PURPOSE OF THE STUDY: The purpose of our study was to compare the clinical, functional and radiological results of two types of tibial components for the same total knee prosthesis (posterior stabilized HLS), all-polyethylene (group A) and metal-backed (group B), in order to answer the following question: does use of an all-polyethylene piece affect mid-term outcome of total knee arthroplasty (TKA)? MATERIAL AND METHODS: This was a retrospective comparative analysis of a single-center non-randomized consecutive series of 169 patients with an all-polyethylene posterior stabilized cemented gliding TKA. This series was matched with another retrospective series of 169 posterior stabilized cemented TKA with a metal-backed tibial piece. Matching factors were age, gender, etiology, and follow-up. The two series were extracted from our database which included all patients who underwent surgery for a TKA in the same institution (Lyon Civil Hospices) performed by one of the authors (PN) or under his responsibility between 1987 and 1996 for group A (all-poly) and between 1987 and 1997 for group B (metal-backed). Mean follow-up was 66 months. The IKS scores and radiological findings were recorded. RESULTS: In group A, 96% of patients were satisfied, 93% in group B. The IKS knee score for group A was 89 +/- 10.8 and 88.3 +/- 11.9 for group B. The function score was 68 +/- 23.7 in group A and 71 +/- 24 in group B. Mean flexion was 113 degrees for both groups. Non-progressive lucent lines were noted in 27 cases in group A and 23 in group B. Revision TKA was performed for 18 knees in group A, including six with implant replacement (three of them for infection). In group B, there were ten revisions, seven with implant replacement including one with infection and three without implant replacement. The 10-year survival was 94.5% in group A and 93.64% in group B. There was no significant difference in the function and knee scores, the presence of lucent lines, and the number of implant replacements between group A and group B (p>0.05). DISCUSSION: This study was unable to demonstrate any superiority in clinical and radiological results for TKA between the all-polyethylene and metal-backed options at five years follow-up.

Characterisation of human knee meniscus cell phenotype.

OBJECTIVE: Studies on the biology of the human meniscus cell are scarce. The objective of our studies was to assess survival/proliferation of human meniscus cells in different culture conditions and to characterize the extracellular matrix (ECM) produced by these cells in these artificial environments. The composition of this ECM offers a variable to define the distinct meniscus cell phenotype. MATERIALS AND METHODS: Human meniscus cells were isolated enzymatically from visually intact lateral and medial knee menisci. Cells were cultured in monolayer conditions or in alginate gel. The composition of the cell-associated matrix (CAM) accumulated by the isolated cells during culture was investigated and compared to the CAM of articular chondrocytes cultured in alginate using flow cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies against type I collagen, type II collagen and aggrecan. Additional cell membrane markers analysis was performed to further identify the different meniscus cell populations in the alginate culture conditions and meniscus tissue sections. Proliferation was analyzed using the Hoechst 33258 dye method. In some experiments, the effect of TGFbeta1 on some of these variables was investigated. RESULTS: The CAM of monolayer cultured meniscus cells is composed of high amounts of type I and II collagen and low amounts of aggrecan. A major population of alginate cultured meniscus cells on the other hand synthesized a CAM containing high amounts of type I collagen, low amounts of type II collagen and high amounts of aggrecan. This population is CD44+CD105+CD34-CD31-. In contrast, a minor cell population in the alginate culture did not accumulate ECM and was mainly CD34+. The CAM of alginate cultured articular chondrocytes is composed of low amounts of type I collagen, high amounts of type II collagen and aggrecan. The expression of aggrecan and of type II collagen was increased by the addition of TGFbeta1 to the culture medium. The proliferation of meniscus cells is increased in the monolayer culture conditions. Cell numbers decrease slightly in the alginate culture, but can be increased after the addition of TGFbeta1. CONCLUSION: These results demonstrate that the human meniscus is populated by different cell types which can be identified by a distinct CAM composition and membrane marker expression. Unlike the monolayer culture conditions, the alginate culture conditions appear to favor a more fibrochondrocyte-like cell accumulating a CAM resembling the native tissue composition. This CAM composition is distinctly different from the CAM composition of phenotypically stable articular cartilage chondrocytes cultured in the same alginate matrix.