F F Hennig

Universitätsklinikum Erlangen, Erlangen, Bavaria, Germany

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Publications (80)143.46 Total impact

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    ABSTRACT: The aim of this retrospective cohort study is to investigate the association between different subjective and objective assessments of ankle function in a population of athletes with or without functional ankle instability (FAI).29 athletes with a history of ankle spraining were divided into two groups according to their ankle status: 16 with FAI (initial ankle sprain with residual functional instability) (age 24.6 ± 3.1 years), and 13 COPERS (initial ankle sprain without residual instability) (age 25.3 ± 4.4 years). The assessment of each individual's ankle function was based on three approaches: The ‘functional-ankle-ability-measure’(FAAM) assessing subjective ankle functionality, measures of sensorimotor control as objective functional measurements and MRI-based T2-mapping as a quantitative marker of compositional joint status. Pearson's product-moment-correlation coefficient, student's t-test and analysis-of-variance were used for statistical analysis. Significant group differences existed for subjective ankle function (FAAM, p=0.04) and MRI-data mainly in the medial compartment of the ankle joint (p≤0.05). We found unique associations between T2-mapping results and sensorimotor scores in the COPER (r=-0.756-0.849), and ‘FAI’-group (r=0.630-0.657). The location and magnitude differed between groups. No correlations existed between these measures and the FAAM.This exploratory study provides preliminary evidence for potential interrelations between various diagnostic measures of ankle function and structure in individuals with and without FAI. We found associations between MRI-results and selected measures of sensorimotor control, indicating a potential link between loss of ankle function and early joint degeneration. Despite these interrelations, each of the different assessment options appears to contain unique information on ankle functionality important in a clinical assessment. This article is protected by copyright. All rights reserved
    No preview · Article · Aug 2015 · Journal of Orthopaedic Research
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    ABSTRACT: 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 occurence of cellular outgrowth from articular cartilage explants isolated from adult human donors. 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 occurence of cellular outgrowth was analysed by histological examination after a culture period of 4 weeks. 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. 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. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Aug 2015 · Osteoarthritis and Cartilage
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    ABSTRACT: Sternal fractures are rare with 3-8 % out of the total number of trauma cases mostly caused by direct impact to the anterior chest wall. Most cases described are due to motor vehicle crash either caused by direct impact to the steering wheel or by the seat belt. Fractures mainly occur to the sternal body. Only rarely are cases of manubrium fractures described in literature, for example, in relationship with a direct impact to the shoulder which caused an oblique fracture near to the sternoclavicular joint. Three patients with profoundly dislocated oblique manubrium fracture were admitted to our Level I Trauma Center in 2012 and 2013. Those patients suffered from instability of the upper sternum and the shoulder girdle. Between January 2012 and October 2013, a total of 538 trauma patients were admitted to the emergency room and received whole body CT-scan. They were analysed retrospectively for sternal fractures. In cases of instability and dislocation, fracture stabilisation was performed by anterior plating through a medial approach using low profile titanium plates (MatrixRib®). Seventy-nine (14.7 %) patients showed sternal fracture, out of which 13 (2.4 %) patients showed a fracture of manubrium, ten caused by seatbelt. In three cases stabilization was performed. Follow up showed sufficient consolidation without complications. A total of 16.5 % of sternal fractures were localized at the manubrium, mostly caused by seat belt. Fractures without significant dislocation seemed to be stable and healed well under conservative treatment. Dislocation in this region leads to unstable shoulder girdle. Anterior plating provides sufficient stabilisation and allowed consolidation.
    Full-text · Article · May 2015 · International Orthopaedics
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    ABSTRACT: The purpose of this study was to investigate integration and cellular outgrowth of native cartilage autografts transplanted into articular cartilage defects. Native cartilage autografts were applied into chondral defects in the femoral condyle of adult sheep. Within the defects, the calcified cartilage layer was either left intact or perforated to induce bone marrow stimulation. Empty defects served as controls. The joints were analyzed after 6 and 26 weeks by macroscopic and histological analysis using the ICRS II Score and Modified O'Driscoll Scores. Non-treated defects did not show any endogenous regenerative response and bone marrow stimulation induced fibrous repair tissue. Transplanted native cartilage grafts only insufficiently integrated with the defect borders. Cell death and loss of proteoglycans were present at the margins of the grafts at 6 weeks, which was only partially restored at 26 weeks. Significant cellular outgrowth from the grafts or defect borders could not be observed. Bonding of the grafts could be improved by additional bone marrow stimulation providing ingrowing cells that formed a fibrous interface predominantly composed of type I collagen. Transplanted native cartilage grafts remain as inert structures within cartilage defects and fail to induce integrative cartilage repair which rather demands additional cells provided by additional bone marrow stimulation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
    Full-text · Article · Mar 2015 · Journal of Orthopaedic Research
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    ABSTRACT: Different ways to stabilize a sternal fracture are described in literature. Respecting different mechanisms of trauma such as the direct impact to the anterior chest wall or the flexion-compression injury of the trunk, there is a need to retain each sternal fragment in the correct position while neutralizing shearing forces to the sternum. Anterior sternal plating provides the best stability and is therefore increasingly used in most cases. However, many surgeons are reluctant to perform sternal osteosynthesis due to possible complications such as difficulties in preoperative planning, severe injuries to mediastinal organs, or failure of the performed method. This manuscript describes one possible safe way to stabilize different types of sternal fractures in a step by step guidance for anterior sternal plating using low profile locking titanium plates. Before surgical treatment, a detailed survey of the patient and a three dimensional reconstructed computed tomography is taken out to get detailed information of the fracture’s morphology. The surgical approach is usually a midline incision. Its position can be described by measuring the distance from upper sternal edge to the fracture and its length can be approximated by the summation of 60 mm for the basis incision, the thickness of presternal soft tissue and the greatest distance between the fragments in case of multiple fractures. Performing subperiosteal dissection along the sternum while reducing the fracture, using depth limited drilling, and fixing the plates prevents injuries to mediastinal organs and vessels. Transverse fractures and oblique fractures at the corpus sterni are plated longitudinally, whereas oblique fractures of manubrium, sternocostal separation and any longitudinally fracture needs to be stabilized by a transverse plate from rib to sternum to rib. Usually the high convenience of a patient is seen during follow up as well as a precise reconstruction of the sternal morphology.
    Full-text · Article · Jan 2015 · Journal of Visualized Experiments
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    S Grupp · V Fürst · P Oppel · F F Hennig · S Schulz-Drost
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    ABSTRACT: Fragestellung: Die beidseitige Rippenserienstückfraktur führt zu einer erheblichen Instabilität des gesamten Brustkorbs und ist mit einer hohen Letalität vergesellschaftet. Diese hochgradig instabilen Verletzungen stellen eine Herausforderung der Versorgung dar und bedürfen vergleichsweise häufig einer operativen Stabilisierung der Brustwand, in der Intention, möglichst physiologische Verhältnisse der Form und Statik wieder herzustellen. Da solche Operationen selten sind, verschiedene Vorgehensweisen beschrieben wurden und technisch anspruchsvoll sind, wurde die Frage nach Möglichkeiten der operativen Versorgung und deren Effektivität im Bereich der anterolateralen Brustwand gestellt. Material und Methoden: Von 12 menschlichen Kadaverpräparaten wurde der gesamte Weichteilmantel entfernt, sodass die reine knöcherne Brustwand mit ihren Intercostalräumen beurteilbar wurde. Der natürliche Ausgangspunkt der Sternumlage wurde als Nullpunkt (NP) festgelegt und mittels einer Messlatte markiert. Sternal wurde im 4.ICR eine digitale Sonde für Druck- und Zugkräfte (PCE-FB, extern, 1kN) fixiert um eine Stabilitätskontrolle durchführen zu können. Nativ und bei jeder Materialkombination wurden Messwerte unter sternaler Auslenkung in 1, 2, 3, 4 und 5 cm sagittaler Entfernung vom NP erhoben. Es wurden serielle Osteotomien der Rippen 2 bis 8 an jeweils zwei Lokalisationen durchgeführt, um einen beidseitigen Rippenserienstückbruch und somit eine instabile Situation zu simulieren. Anschließend erfolgte die Stabilisierung durch unterschiedliche Implantate: Transsternal, quer eingeschlagener Metallbügel (CrV, Firma Lettenbauer) Verschiedene Kombinationen einer winkelstabilen Plattenosteosynthese (MatrixRib®, Synthes). Ergebnisse: Im Zuge o. g. Osteotomien kam es zu einem Einsinken des Sternums um bis zu 75mm vom NP, einer maximal instabilen Situation entsprechend. Je nach Materialkombination gelang eine vollständige Wiederaufrichtung der imprimierten Brustwand bzw. bis nahe an den NP heran. Jedoch konnten weit lateral gelegene Frakturen durch den Bügel nicht suffizient abgestützt werden. Dieses vermochte nur die Plattenosteosynthese, die lateral gelegene Rippenstückbrüche überbrückte, die Brustwand anatomisch rekonstruierte, ein s.g. Realignement, und die Einsinktiefe in allen Fällen verminderte. Außerdem konnten nahezu ähnliche physiologische Verhältnisse wieder hergestellt werden, im Sinne einer dreidimensionalen Verformbarkeit während eines Atemzyklus. Die Stabilität der instabilen Brustwand wurde durch die Osteosynthese erheblich verbessert. Unsere Materialkombinationen zeigten eine Stabilität von bis zu 60 % der nativen Stabilität. Je mehr Rippen osteosynthetisch versorgt wurden, desto höher war die Stabilität der Brustwand. Da der Bügel sich extraanatomisch auf den Rippen abstützt und somit die Brustwand anhebt, vermochte er kein Realignement dislozierender Rippen zu vermitteln und damit auch keine physiologischen Verhältnisse. Diskussion: Es gilt, die Frage der Belastbarkeit und die Möglichkeit der dreidimensionalen Verformbarkeit im Rahmen des Atemzyklus und externer Kompression zu beantworten. Die beidseitige Rippenserienstückfraktur führt zu einer erheblichen Instabilität welche v. a. von der Lokalisation der Rippenfrakturen, der Anzahl und dem Muster abhängig ist.
    Full-text · Conference Paper · Oct 2014
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    S Schmitt · S Grupp · P Oppel · F F Hennig · S Schulz-Drost
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    ABSTRACT: Fragestellung: Sternumfrakturen (SF) werden als seltene Entität mit etwa 3-8% Häufigkeit aller Frakturen beschrieben. Entstehen können sie z.B. durch ein direktes Anpralltrauma, sowie eine ruckartige Flexionsoder Extensionsbewegung des Rumpfes im Rahmen verschiedenster Unfallmechanismen. Eine zunehmende Rolle spielen auch osteoporotische Frakturen. In der Literatur sind unterschiedliche Beschreibungen hinsichtlich der Altersverteilung beschrieben. In der Regel werden Verteilungen nur aus monozentrisch erhobenen Daten dargestellt. Angaben über die bundesweite Altersverteilung der SF wurden nach unserer Kenntnis bislang nicht publiziert. Ziel dieser Arbeit ist des daher, eine Übersicht der deutschlandweit stationär behandelten SF darzustellen, sowie Aussagen über die Altersverteilung treffen zu können. Datenquelle Statistisches Bundesamt, Zweigstelle Bonn, H101-Krankenhausstatistik Die Versorgungsrealität von Sternumfrakturen in der BRD – Eine systematische epidemiologische Analyse der Jahre 2005-2012 S. Schmitt, S. Grupp, P. Oppel, F.F. Hennig, S. Schulz-Drost Material und Methode: Es wurde mit Unterstützung des Statistischen Bundesamtes eine systematische Analyse von Daten aller Krankenhäuser von 2005 bis 2012, die nach dem DRG-Vergütungssystem abrechnen und dem Anwendungsbereich des §1 KHEntgG unterliegen, für folgende Diagnosen durchgeführt: S22.2 in der Rolle der Haupt- und Nebendiagnose (HD, ND) Ausgewertet wurde die Altersverteilung der stationär behandelten Patienten. Ergebnisse: Insgesamt wurden 47893 Patienten in Deutschland zwischen 2005 und 2012 aufgrund von SF (jährlicher MW = 5986, min. 5719, max. 6337, SD 218) stationär behandelt, davon 24960 mit SF als HD und 22933 als ND. Die Verteilung über die Jahre ist nahezu gleich, wobei im Trend eine Abnahme der SF als HD und eine Zunahme der SF als ND zu beobachten ist. Unter 25J haben mehr Pat. eine SF als HD, nach dem 25. Lj sind die Verhältnisse von HD und ND ausgeglichen. Im kindlichen Alter ist die SF mit einem Anteil von 1,83% vor dem 16.Lj eine Rarität, nach dem 16.Lj ist ein sprunghafter Anstieg der Häufigkeit bis zum 20.Lj zu sehen, dann bis zum 35. Lj ein Rückgang der Häufigkeit, bevor diese bis zum 80.Lj wieder ansteigt, mit Altersgipfeln um 55J, 72J und 80J. Über 65-jährige machen 43.3% der Gesamt-SF aus. Diskussion: Der sprunghafte Anstieg der SF nach dem 16.Lj kann nach Abgleich mit altersabhängigen Unfallstatistiken der vermehrten Unfallquote dieser Altersgruppe, z.B. bei frisch erworbenem Führerschein uä., zuzuschreiben sein. Im Erwachsenenalter (ca.25-39J) sind die SF eher selten, bei in der Regel körperlicher Gesundheit und geringerem Unfallrisiko. Der anschließende Anstieg der SF kann durch ein wieder erhöhtes Unfallrisiko erklärt werden und vor allem durch einen steigenden Anteil von Altersfrakturen aufgrund zunehmenden Osteoporoserisikos. Der zweite Anstieg nach dem 35.Lj wird jedoch noch einmal durch einen Rückgang bei der Altersgruppe der 60-65 Jährigen unterbrochen. Diese lässt sich nach Abgleich mit Verkehrsteilnehmerstatistiken am ehesten darauf zurückführen, dass die Beteiligung an PKW-Verkehrsunfällen in der Altersgruppe der 55-65 Jährigen stark rückläufig ist. Schlussfolgerung: Schlussfolgernd ermöglichen DRG-basierte Daten der Krankenhäuser in der BRD, ein stationär behandeltes Krankheitsbild nach dessen Altersverteilung zu charakterisieren. Im vorliegenden Beispiel konnte die Sternumfraktur nach ihrer Altershäufigkeitin der ganzen BRD beschrieben werden.
    Full-text · Conference Paper · Oct 2014
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    ABSTRACT: New noninvasive biochemical quantitative magnetic resonance imaging (MRI) techniques are increasingly applied in cartilage repair and osteoarthritis (OA), where quantitative T2 mapping and initially also T2* mapping are seen as valid biomarkers. These quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by increasing water content and a disruption of the collagen network. Recently, feasibility of biochemical MR imaging of repair tissue and the surrounding cartilage after cartilage repair procedures has been demonstrated. Different ultrastructural properties of the repair tissue after different repair procedures, such as microfracturing and autologous chondrocyte implantation, resulted in differences in imaging characteristics. Further, these biochemical imaging characteristics varied during follow-up and are able to depict repair tissue maturation. Within these approaches, zonal stratification analysis was considered crucial. Comparably in OA, T2 mapping seems to provide additional information during different stages of cartilage degeneration and can be used in patient subgroups as a predictor for disease progression. Although the results in various studies employing T2 and T2* mapping are very promising and valuable additional information on cartilage ultrastructure can be obtained, (comparable to all the other quantitative cartilage imaging techniques) further multimodal investigation is needed especially since a standard of reference is hard to define.
    Preview · Article · Aug 2014
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    ABSTRACT: Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA)Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level.Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (≥3years) and those with ACPA positivity than those with a short disease duration (<3 years)(p=0.034) or negative ACPA (p=0.0002), respectively. In contrast, no association between cartilage proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found.Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA. © 2014 American College of Rheumatology.
    Full-text · Article · Aug 2014 · Arthritis and Rheumatology
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    ABSTRACT: The aim of this study was to investigate, using T2-mapping, the impact of functional instability in the ankle joint on the development of early cartilage damage. Ethical approval for this study was provided. Thirty-six volunteers from the university sports program were divided into three groups according to their ankle status: functional ankle instability (FAI, initial ankle sprain with residual instability); ankle sprain Copers (initial sprain, without residual instability); and controls (without a history of ankle injuries). Quantitative T2-mapping MRI was performed at the beginning ('early-unloading') and at the end ('late-unloading') of the MR-examination, with a mean time span of 27min. Zonal region-of-interest T2-mapping was performed on the talar and tibal cartilage in the deep and superficial layers. The inter-group comparisons of T2-values were analyzed using paired and unpaired t-tests. Statistical analysis-of-variance was performed. T2-values showed significant to highly significant differences in 11 of 12 regions throughout the groups. In early-unloading, the FAI-group showed a significant increase in quantitative T2-values in the medial, talar regions (p=0.008,p=0.027), whereas the Coper-group showed this enhancement in the central-lateral regions (p=0.05). Especially the comparison of early-loading to late-unloading values revealed significantly decreasing T2-values over time laterally and significantly increasing T2-values medially in the FAI-group, which were not present in the Coper- or control-group. Functional instability causes unbalanced loading in the ankle joint, resulting in cartilage alterations as assessed by quantitative T2-mapping. This approach can visualize and localize early cartilage abnormalities, possibly enabling specific treatment options to prevent osteoarthritis in young athletes.
    Full-text · Article · May 2014 · Osteoarthritis and Cartilage

  • No preview · Article · Apr 2014 · Osteoarthritis and Cartilage
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    ABSTRACT: Objective The aim of this study was to investigate, using T2-mapping, the impact of functional instability in the ankle joint on the development of early cartilage damage. Methods Ethical approval for this study was provided. Thirty-six volunteers from the university sports program were divided into three groups according to their ankle status: functional ankle instability (FAI, initial ankle sprain with residual instability); ankle sprain Copers (initial sprain, without residual instability); and controls (without a history of ankle injuries). Quantitative T2-mapping MRI was performed at the beginning (’early-unloading’) and at the end (’late-unloading’) of the MR-examination, with a mean time span of 27min. Zonal region-of-interest T2-mapping was performed on the talar and tibal cartilage in the deep and superficial layers. The inter-group comparisons of T2-values were analyzed using paired and unpaired t-tests. Statistical analysis-of-variance was performed. Results T2-values showed significant to highly significant differences in 11 of 12 regions throughout the groups. In early-unloading, the FAI-group showed a significant increase in quantitative T2-values in the medial, talar regions (p=0.008,p=0.027), whereas the Coper-group showed this enhancement in the central-lateral regions (p=0.05). Especially the comparison of early-loading to late-unloading values revealed significantly decreasing T2-values over time laterally and significantly increasing T2-values medially in the FAI-group, which were not present in the Coper- or control-group. Conclusion Functional instability causes unbalanced loading in the ankle joint, resulting in cartilage alterations as assessed by quantitative T2-mapping. This approach can visualize and localize early cartilage abnormalities, possibly enabling specific treatment options to prevent osteoarthritis in young athletes.
    Full-text · Article · Jan 2014 · Osteoarthritis and Cartilage
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    ABSTRACT: Operative treatment of sternal fractures has become a matter of increasing interest. Anterior plating seems to be the most appropriate method for fixing sternal fractures. However, there are several concerns in relation to the operative procedure such as severe injuries to mediastinal organs, patient comfort and proper stabilisation, for example. This paper describes a safe method of anterior sternal plating using locked plate fixation with limited depth drilling. Ten patients with sternal fractures were included in this cohort study and were treated by anterior plating using one or two plates in parallel through a median approach to the sternum. Follow up was performed after six weeks, 12 weeks and six months. Follow up revealed no serious complications. One patient suffered from postoperative wound seroma. No problems were caused by the plates. Sternal plating using low profile locked titanium plates seems to be a safe and stable method with a high level of patient comfort.
    Full-text · Article · Oct 2013 · International Orthopaedics
  • Goetz H. Welsch · Friedrich F. Hennig · Andreas Mauerer
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    ABSTRACT: Articular cartilage injuries are common findings within different joints and patients benefit from optimal diagnosis and treatment. Magnetic resonance imaging (MRI) has become the method of choice for diagnosis of chondral injuries and for the follow-up of patients after cartilage repair surgery. Comparably in degenerative cartilage diseases, MRI is getting more and more important in the description and especially the quantification of the cartilage loss/damage. Here besides the morphological description of the specific cartilage pathology, the assessment of the biochemical status of the cartilage is in the focus of recent research as well as clinical applications. Thus, early and precise diagnosis of ultra-structural cartilage alterations, together with modern surgical treatment options, may offer a possibility for patients with cartilage defects to avoid OA or to delay the progression of OA. The present article provides an overview of issues around the use of biochemical imaging in the clinic setting in the knee and the hip joint. The current state of the art of biochemical MRI in patients with cartilage injuries or after cartilage repair will be discussed as well as the use of biochemical MR techniques in early OA and degenerative cartilage changes. The ultra-structure of repair cartilage can be assessed noninvasively by means of biochemical MRI techniques such as delayed Gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 mapping, T1 rho, diffusion-weighted imaging, or other techniques. These new MR methodologies as well as their sensitivity to specific components of articular cartilage will be provided and discussed in a clinical background.
    No preview · Article · Jul 2013
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    ABSTRACT: To identify factors that are responsible for the phenotypic differences between transient chondrocytes within human osteophytes prone to endochondral ossification and permanent chondrocytes within articular cartilage persisting for decades. Differential gene expression of chondrocytes from human osteophytes or from articular cartilage was detected by cDNA microarray analysis. The expression of pigment epithelium-derived factor (PEDF), one of the most impressively differentially expressed genes, was validated by quantitative reverse transcriptase polymerase chain reaction as well as immunohistochemistry. The mode of action of PEDF was explored by cell viability assays and by detecting target genes. PEDF mRNA expression was upregulated by 118.5-fold (P = 0.01) in human osteophytic cartilage compared with articular cartilage, which was reflected by strong immunostaining for PEDF in the cartilaginous layer of osteophytes but largely negative staining in articular cartilage. Elevated levels of PEDF in osteophytes were associated with enhanced apoptosis. PEDF increased the expression of the proapoptotic factor FasL and induced cell death in cell culture. Osteochondral progenitor cells were more responsive to PEDF than differentiated articular chondrocytes. The induction of the proapoptotic factor PEDF within the osteophyte cartilage suggests a molecular concept for the transient chondrocyte phenotype that arises from progenitor cells and is prone to terminal differentiation and cell death.
    Full-text · Article · Jul 2013 · Cartilage
  • Goetz H. Welsch · Friedrich F. Hennig · Siegfried Trattnig
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    ABSTRACT: Articular cartilage injuries are common findings within different joints and patients benefit from optimal diagnosis and treatment. Magnetic resonance imaging (MRI) has become the method of choice for diagnosis of chondral injuries and for the follow-up of patients after cartilage repair surgery. Thus, early and precise diagnosis together with surgical treatment options may offer a possibility for patients with cartilage defects to avoid OA or to delay the progression of OA. Therefore, widespread cartilage repair techniques, including arthroscopic or open surgical approaches as well as marrow-stimulation techniques, osteochondral grafting, and chondrocyte implantation/transplantation, require knowledgeable and high quality follow-up. The present chapter provides an overview of the current state of the art of MRI in patients with cartilage injuries or after cartilage repair. Initially an overview about the pre-requirements of high quality MR imaging of articular cartilage and its repair will be provided. Then cartilage sensitive MR protocols will be introduced and described including basic MR sequences and new three-dimensional isotropic approaches. Morphological post-operative cartilage repair MR imaging will be provided, again based on standard and advanced MR techniques. Special focus will be given on post-operative scoring with the MR observation of cartilage repair tissue (MOCART) score. Furthermore the ultra-structure of the repair tissue and the surrounding cartilage can be assessed non-invasively by means of biochemical MRI techniques such as delayed Gadolinium enhanced MRI of cartilage (dGEMRIC), T2 mapping, T1 rho, diffusion weighted imaging or other techniques. These new MR methodologies as well as their sensitivity to specific components of articular cartilage and the repair tissue will be provided and discussed. Additionally examples of other advanced or future options will be given, such as biomechanical MRI approaches and MRI of animal models after cartilage repair. Concluding the differences of the various cartilage repair techniques with respect to their imaging appearance will be presented and discussed. Bringing these advanced MR imaging methods into the diagnosis and treatment of cartilage injuries and repair, new insight will be given non-invasively which can be used in clinical routine, scientific studies and during clinical trials.
    No preview · Article · Jun 2013
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    K Gelse · A.B. Ekici · F Cipa · B Swoboda · H D Carl · A Olk · F F Hennig · P Klinger
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    ABSTRACT: To identify the molecular differences between the transient and permanent chondrocyte phenotype in osteophytic and articular cartilage. 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. 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. 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.
    Full-text · Article · Dec 2011 · Osteoarthritis and Cartilage
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    ABSTRACT: Hypoxia-inducible factors (HIF1α/HIF2α) are key transcription factors that promote angiogenesis. The overexpression of degradation-resistant HIF mutants is considered a promising pro-angiogenic therapeutic tool. We compared the transcriptional activity of HIF1α/HIF2α mutants that obtained their resistance to oxygen-dependent degradation either by deletion of their entire oxygen-dependent degradation (ODD) domain or by replacement of prolyl residues that are crucial for oxygen-dependent degradation. Although all HIF mutants translocated into the nucleus, HIF1α and HIF2α mutants inclosing the point mutations were significantly more effective in trans-activating the target gene VEGF and in inducing tube formation of endothelial cells than mutants lacking the complete ODD domain.
    Full-text · Article · Nov 2011 · Transcription
  • A Neuhof · F F Hennig · I Schöffl · V Schöffl
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    ABSTRACT: The aim of this study was to quantify and rate acute sport climbing injuries. Acute sport climbing injuries occurring from 2002 to 2006 were retrospectively assessed with a standardized web based questionnaire. A total number of 1962 climbers reported 699 injuries, which is equivalent to 0.2 injuries per 1 000 h of sport participation. Most (74.4%) of the injuries were of minor severity rated NACA I or NACA II. Injury distribution between the upper (42.6%) and lower extremities (41.3%) was similar, with ligament injuries, contusions and fractures being the most common injury types. Years of climbing experience (p<0.01), difficulty level (p<0.01), climbing time per week during summer (p<0.01) and winter (p<0.01) months were correlated with the injury rate. Age (p<0.05 (p=0.034)), years of climbing experience (p<0.01) and average climbing level (p<0.01) were correlated to the injury severity rated through NACA scores. The risk of acute injuries per 1 000 h of sport participation in sport climbing was lower than in previous studies on general rock climbing and higher than in studies on indoor climbing. In order to perform inter-study comparisons of future studies on climbing injuries, the use of a systematic and standardized scoring system (UIAA score) is essential.
    No preview · Article · Sep 2011 · International Journal of Sports Medicine
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    ABSTRACT: To investigate the effect of chondromodulin 1 on the phenotype of osteochondral progenitor cells in cartilage repair tissue. Self-complementary adeno-associated virus (AAV) vectors carrying chondromodulin 1 complementary DNA (AAV-Chm-1) were applied to cartilage lesions in the knee joints of miniature pigs that were treated by the microfracture technique. Alternatively, isolated porcine osteochondral progenitor cells were infected with AAV-Chm-1 or with AAV-GFP control vectors ex vivo prior to being transplanted into cartilage lesions in which the subchondral bone plate was left intact. The quality of the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods. The effects of chondromodulin 1 overexpression were also analyzed by angiogenesis assays and quantitative reverse transcriptase-polymerase chain reaction. AAV-Chm-1-infected cells efficiently produced chondromodulin 1, which had strong antiangiogenic effects, as verified by the inhibition of tube formation of endothelial cells. Gene expression analyses in vitro revealed the cell cycle inhibitor p21WAF1/Cip1 as one target up-regulated by AAV-Chm-1. Direct application of AAV-Chm-1 vectors into microfractured porcine cartilage lesions stimulated chondrogenic differentiation of ingrowing progenitor cells, but significantly inhibited terminal chondrocyte hypertrophy, the invasion of vessel structures, and excessive endochondral ossification, which were otherwise observed in untreated lesions. Indirect gene transfer, with infection of porcine osteochondral progenitor cells by AAV-Chm-1 ex vivo, also supported chondrogenic differentiation of these transplanted cells. AAV-Chm-1-infected cells maintained a chondrocyte-like phenotype and formed a hyaline-like matrix that was superior to that formed by uninfected or AAV-GFP-infected cells. Our findings indicate that the antiangiogenic factor chondromodulin 1 stabilizes the chondrocyte phenotype by supporting chondrogenesis but inhibiting chondrocyte hypertrophy and endochondral ossification.
    Full-text · Article · Sep 2011 · Arthritis & Rheumatology

Publication Stats

690 Citations
143.46 Total Impact Points

Institutions

  • 2003-2015
    • Universitätsklinikum Erlangen
      • • Department of Surgery
      • • Unfallchirurgische Abteilung
      Erlangen, Bavaria, Germany
  • 2000-2015
    • Friedrich-Alexander-University of Erlangen-Nürnberg
      • Department of Surgery
      Erlangen, Bavaria, Germany
  • 2009
    • Sozialstiftung Bamberg/Klinikum Bamberg
      Bamberg, Bavaria, Germany
    • University of Wuerzburg
      • Institute of Pharmacy and Food Chemistry
      Würzburg, Bavaria, Germany