Limited evidence of chondrocyte outgrowth from adult human articular cartilage.

OBJECTIVE: Cellular outgrowth from articular cartilage tissue has been described in a number of recent experimental studies. The aim of this study was to investigate the occurrence of cellular outgrowth from articular cartilage explants isolated from adult human donors. METHOD: Macroscopically intact articular cartilage specimens were isolated from adult human donors and cultured either in their native status, or in a cleansed status achieved by forced washing to minimize attaching cells. Additionally, the effect of chemotactic stimuli including cell lysate, High-Mobility-Group-Protein B1 (HMGB-1), Trefoil-factor 3 (TFF3), bone morphogenetic protein-2 (BMP-2), transforming growth factor-ß1 (TGF-ß1), or three-dimensional fibrin or collagen matrices were investigated. Co-cultures with synovial membrane served as a positive control for a source of migratory cells. The occurrence of cellular outgrowth was analyzed by histological examination after a culture period of 4 weeks. RESULTS: Spontaneous cellular outgrowth from cleansed cartilage specimens was not observed at a relevant level and could not significantly be induced by chemotactic stimuli or three-dimensional matrices either. A forming cartilage-adjoining cell layer was only apparent in the case of native cartilage explants with cellular remnants from surgical isolation or in co-culture experiments with synovial membrane. CONCLUSION: The relevance of cellular outgrowth from cartilage tissue is largely absent in the case of adult human articular cartilage samples. A cartilage-adjoining cell layer forming around the explants may instead originate from still attaching cells that remained from surgical isolation.

[Pigmented villonodular synovitis. A rare differential diagnosis of synovial joint swelling]. / Pigmentierte villonoduläre Synovialitis. Eine seltene Differenzialdiagnose der synovialen Gelenkschwellung.

BACKGROUND: Pigmented villonodular synovitis (PVNS) describes a rare disease caused by an abnormal proliferation of the synovial membrane in large and small joints. In order to achieve an optimal result of treatment it is necessary to carry out specific diagnostics and a targeted therapy approach. OBJECTIVE: This article gives a review of the epidemiology, etiopathogenesis and diagnostic management of PVNS as well as presenting the current therapy and treatment recommendations. MATERIAL AND METHODS: A systematic search of the literature was performed in the databank of the National Center for Biotechnology Information ( http://www.ncbi.nlm.nih.gov/pubmed ). The search targeted randomized clinical and experimental studies, systematic and non-systematic review articles, expert opinions and case reports related to PVNS, independent of the level of evidence attained by each study. RESULTS: The differential diagnosis of PVNS should be considered in cases of recurrent hemorrhagic joint effusions. The cause of the disease has not yet been exactly clarified. The final diagnosis can ultimately only be confirmed by histological investigations. In order to obtain representative histological tissue samples for the diagnosis, magnetic resonance imaging (MRI) with the appropriate heme sequences should be carried out prior to taking samples. The management of PVNS is often difficult due to the high risk of recurrence depending on the various forms. In view of the high rate of recurrence, therapy should include a complete synovectomy. CONCLUSION: For the surgical approach arthroscopic and open procedures have been described, which are currently controversially discussed with respect to the complication and recurrence rates. Adjuvant interventional therapy forms, such as radiosynoviorthesis are recommended to reduce the recurrence rate.

[Recovery of knee function after total knee arthroplasty: different outcomes in patients with osteoarthritis and rheumatoid arthritis]. / Gelenkfunktion nach bikondylärer Knieendoprothese: Unterschiedlicher Verlauf bei Patienten mit Gonarthrose und rheumatoider Arthritis.

INTRODUCTION: Following total knee arthroplasty (TKA), no investigations have been published to assess possible differences between rheumatoid arthritic (RA) and osteoarthritic (OA) patients with respect to patient-reported outcome measures of knee function. PATIENTS AND METHODS: A cohort of 128 consecutively operated patients (OA: n = 92, RA: n = 36) treated with bicondylar TKA was included in this prospective, clinical study. Knee function was assessed preoperatively and at 6 and 12 months after TKA, using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Oxford Knee Score (OKS). RESULTS: Both OKS and KOOS revealed a statistically significant improvement for OA and RA patients at 6 and 12 months after surgery, as compared to the preoperative status. The results of the OKS at 6 and 12 months did not show a further improvement for either group. The KOOS, however, revealed an additional improvement between 6 and 12 months for the osteoarthritis group, regarding the total score and all subscores, but not for the RA subgroup. CONCLUSION: Functional recovery after TKA improves in the second 6 months after surgery in OA patients, but not in RA patients, when knee function is exclusively assessed with patient-reported outcome measures.

Molecular differentiation between osteophytic and articular cartilage--clues for a transient and permanent chondrocyte phenotype.

OBJECTIVE: To identify the molecular differences between the transient and permanent chondrocyte phenotype in osteophytic and articular cartilage. METHODS: Total RNA was isolated from the cartilaginous layer of osteophytes and from intact articular cartilage from knee joints of 15 adult human donors and subjected to cDNA microarray analysis. The differential expression of relevant genes between these two cartilaginous tissues was additionally validated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry. RESULTS: Among 47,000 screened transcripts, 600 transcripts were differentially expressed between osteophytic and articular chondrocytes. Osteophytic chondrocytes were characterized by increased expression of genes involved in the endochondral ossification process [bone gamma-carboxyglutamate protein/osteocalcin (BGLAP), bone morphogenetic protein-8B (BMP8B), collagen type I, alpha 2 (COL1A2), sclerostin (SOST), growth arrest and DNA damage-induced gene 45ß (GADD45ß), runt-related transcription factor 2 (RUNX2)], and genes encoding tissue remodeling enzymes [matrix metallopeptidase (MMP)9, 13, hyaluronan synthase 1 (HAS1)]. Articular chondrocytes expressed increased transcript levels of antagonists and inhibitors of the BMP- and Wnt-signaling pathways [Gremlin-1 (GREM1), frizzled-related protein (FRZB), WNT1 inducible signaling pathway protein-3 (WISP3)], as well as factors that inhibit terminal chondrocyte differentiation and endochondral bone formation [parathyroid hormone-like hormone (PTHLH), sex-determining region Y-box 9 (SOX9), stanniocalcin-2 (STC2), S100 calcium binding protein A1 (S100A1), S100 calcium binding protein B (S100B)]. Immunohistochemistry of tissue sections for GREM1 and BGLAP, the two most prominent differentially expressed genes, confirmed selective detection of GREM1 in articular chondrocytes and that of BGLAP in osteophytic chondrocytes and bone. CONCLUSIONS: Osteophytic and articular chondrocytes significantly differ in their gene expression pattern. In articular cartilage, a prominent expression of antagonists inhibiting the BMP- and Wnt-pathway may serve to lock and stabilize the permanent chondrocyte phenotype and thus prevent their terminal differentiation. In contrast, osteophytic chondrocytes express genes with roles in the endochondral ossification process, which may account for their transient phenotype.

[Presurgical and postsurgical orthotic management of the rheumatoid foot]. / Orthopädieschuhtechnische Versorgung vor und nach operativen Eingriffen am Fuß.

Foot complaints remain frequent in patients with rheumatoid arthritis (RA) even in the era of biological anti-rheumatic drugs. Orthotic management of rheumatoid foot disorders is able to improve mobility and thus the quality of life in RA patients. This article highlights the preoperative and postoperative orthotic management of the rheumatoid arthritic foot.

[Total knee arthroplasty for rheumatoid arthritis]. / Endoprothetik des Rheumatischen Kniegelenks.

A total of 150,000 primary total knee arthroplasties are performed in Germany each year. There is only a limited amount of evidence-based data available on possible surgery-related differences between osteoarthritis (OA) and rheumatoid arthritis (RA) of the knee joint. The following review summarizes the recent literature on total knee arthroplasty with a focus on special features of RA patients.

[Insufficiency fractures of the feet and lower limbs in rheumatoid arthritis]. / Insuffizienzfrakturen an Fuß und Unterschenkel bei rheumatoider Arthritis.

BACKGROUND: Insufficiency fractures are generally a rare event, especially of the hindfoot. These are often overlooked in the initial stage, however, they must be regarded as a differential diagnosis in the range of possible causes in patients with rheumatoid arthritis and unclear complaints. MATERIAL AND METHODS: Outpatients in an arthritis care unit from 2009-2011 were analyzed for fractures of the hindfoot and distal tibia. RESULTS: A total of six patients with seven fractures without adequate trauma were found in the cohort. All patients had received disease modifying therapy and corticosteroids. All fractures could be successfully treated without surgery. CONCLUSION: Insufficiency fractures in patients with rheumatoid arthritis are a typical finding after several years of the disease. They are directly related to the disease and medication and can usually be successfully treated conservatively.

Quantitative ultrasound biomicroscopy for the analysis of healthy and repair cartilage tissue.

The increasing spectrum of different cartilage repair strategies requires the introduction of adequate non-destructive methods to analyse their outcome in-vivo, i.e. arthroscopically. The validity of non-destructive quantitative ultrasound biomicroscopy (UBM) was investigated in knee joints of five miniature pigs. After 12 weeks, six 5-mm defects, treated with different cartilage repair approaches, provided tissues with different structural qualities. Healthy articular cartilage from each contralateral unoperated knee joint served as a control. The reflected and backscattered ultrasound signals were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB) parameters. The cartilage repair tissues were additionally assessed biomechanically by cyclic indentation, histomorphologically and immunohistochemically. UBM allowed high-resolution visualisation of the structure of the joint surface and subchondral bone plate, as well as determination of the cartilage thickness and demonstrated distinct differences between healthy cartilage and the different repair cartilage tissues with significant higher IRC values and a steeper negative slope of the depth-dependent backscatter amplitude AIBslope for healthy cartilage. Multimodal analyses revealed associations between IRC and the indentation stiffness. Furthermore, AIBslope and AIB at the cartilage-bone boundary (AIBdC) were associated with the quality of the repair matrices and the subchondral bone plate, respectively. This ex-vivo pilot study confirms that UBM can provide detailed imaging of articular cartilage and the subchondral bone interface also in repaired cartilage defects, and furthermore, contributes in certain aspects to a basal functional characterization of various forms of cartilage repair tissues. UBM could be further established to be applied arthroscopically in-vivo.

[Bacterial infections of the rheumatoid foot]. / Der rheumatische Fuss als Focus bakterieller Infektionen.

BACKGROUND: A high incidence of infections has been reported in rheumatoid arthritis (RA) patients, either due to intrinsic factors or as a side effect of immunosuppressive agents used for treatment. The present article provides an overview of incidence and distribution patterns of septic complications in RA. MATERIALS AND METHODS: We prospectively assessed all data from RA patients who underwent in-patient treatment for septic complications in the 3-year period from 01.01.2006 to 31.12.2009. All disease- and infection-specific data were gathered and analysed. RESULTS: Of the 36 cases in total, infection was localized in the rheumatoid foot in 23 patients (64%) and at the lower extremities in 32 (89%). The bacterial spectrum was heterogenous, with Staphylococcus aureus representing the most frequent causative agent. In total, 34 of 36 cases were cured. CONCLUSIONS: Since approximately 2/3 of all infections occur in the rheumatoid foot, regular foot examinations to identify predisposing deformities and/or ensure early diagnosis of existing infections are recommended.

Transplanted chondrocytes inhibit endochondral ossification within cartilage repair tissue.

The aim of this study was to investigate the effect of transplanted chondrocytes on endochondral bone formation in cartilage repair tissue. In the knee joint of miniature pigs, cartilage lesions were treated by microfracturing and were then either left empty, covered with a collagen membrane, or treated by matrix-associated autologous chondrocyte transplantation. In control lesions, the subchondral bone plate was left intact (partial-thickness lesion). The repair tissues were analyzed after 12 weeks by histological methods focusing on bone formation and vascularization. The effect of chondrocytes on angiogenesis was assessed by in vitro assays. The presence of antiangiogenic proteins in cartilage repair tissue, including thrombospondin-1 (TSP-1) and chondromodulin-I (ChM-I), was detected immunohistochemically and their expression in chondrocytes and bone marrow stromal cells was measured by quantitative RT-PCR. Significant outgrowths of subchondral bone and excessive endochondral ossification within the repair tissue were regularly observed in lesions with an exposed or microfractured subchondral bone plate. In contrast, such excessive bone formation was significantly inhibited by the additional transplantation of chondrocytes. Cartilaginous repair tissue that resisted ossification was strongly positive for the antiangiogenic proteins, TSP-1 and ChM-I, which were, however, not detectable in vascularized osseous outgrowths. Chondrocytes were identified to be the major source of TSP-1- and ChM-I expression and were shown to counteract the angiogenic activity of endothelial cells. These data suggest that the resistance of cartilaginous repair tissue against endochondral ossification following the transplantation of chondrocytes is associated with the presence of antiangiogenic proteins whose individual relevance has yet to be further explored.

Cellular heterogeneity in cultured human chondrocytes identified by antibodies specific for alpha 2(XI) collagen chains.

Collagen type XI is a component of hyaline cartilage consisting of alpha 1(XI), alpha 2(XI), and alpha 3(XI) chains; with 5-10% of the total collagen content, it is a minor but significant component next to type II collagen, but its function and precise localization in cartilaginous tissues is still unclear. Owing to the homology of the alpha 3(XI) and alpha 1(II) collagen chains, attempts to prepare specific antibodies to native type XI collagen have been unsuccessful in the past. In this study, we report on the preparation and use for immunohistochemistry of a polyclonal antibody specific for alpha 2(XI) denatured collagen chains. The antibody was prepared by immunization with the isolated alpha 2(XI) chain and reacts neither with native type XI collagen nor type I, II, V, or IX by ELISA or immunoblotting, nor with alpha 1(XI) or alpha 3(XI), but with alpha 2(XI) chains. Using this antibody, it was possible to specifically localize alpha 2(XI) in cartilage by pretreating tissue sections with 6 M urea. In double immunofluorescence staining experiments, the distribution of alpha 2(XI) as indicative for type XI collagen in fetal bovine and human cartilage was compared with that of type II collagen, using a monoclonal antibody to alpha 1(II). Type XI collagen was found throughout the matrix of hyaline cartilage. However, owing to cross-reactivity of the monoclonal anti-alpha 1(II) with alpha 3(XI), both antibodies produced the same staining pattern. Cellular heterogeneity was, however, detected in monolayer cultures of human chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)