Die Osteoarthrose ist eine degenerative Erkrankung der Gelenke. Sie zeichnet sich durch eine sukzessive Destruktion des Knorpels sowie der umliegenden Strukturen aus. Die Osteoarthrose ist die häufigste Gelenkerkrankung des Menschen und tritt insbesondere im hohen Lebensalter auf. Schätzungen zu Folge wird Osteoarthrose im Jahr 2020 zu der viert häufigsten Ursache für Erwerbsunfähigkeit aufsteigen. Neben dem Leidensdruck für den Patienten ist dies auch mit erheblichen Kosten für das Gesundheitssystem verbunden. Die natürliche Regeneration des avaskulären hyalinen Knorpels ist aufgrund der geringen Zelldichte und dem niedrigen Metabolismus der Zellen beschränkt. Es fehlt ein Perichondrium das den Knorpel stabilisiert und mit undifferenzierten Mesenchymzellen, als Quelle für frische Chondroblasten bzw. Chondrozyten, versorgt. Das fibrokartilaginäre Ersatzgewebe im erkrankten artikulären Knorpel beherbergt eine Population von Vorläuferzellen mit chondrogenen Eigenschaften. Die Herkunft dieser Zellen ist wenig erforscht. Es wird vermutet, dass diese durch Einsprossungen von Blutgefäßen aus dem subchondralen Knochen in die beschädigten Areale migrieren. Diese chondrogenen Progenitorzellen (CPCs) könnten sich als zugänglich für medikamentöse Therapien zur Stimulation ihres Reperaturpotentials erweisen. In dieser Arbeit sollten Coaktivatoren von dem chondrogenen Transkriptionsfaktor SOX9 oder Corepressoren von dem osteogenen Transkriptionsfaktor RUNX2 identifiziert werden. Dazu wurden CPCs verwendet, die durch siRNA-vermittelten Knockdown von RUNX2 in der Produktion von chondrogenen Faktoren stimuliert werden sollten. Auch der umgekehrte Versuch wurde durchgeführt. Durch den Knockdown von SOX9 sollten osteogene Faktoren stimuliert werden, die als Ziel inhibitorischer Therapien dienen könnten. Dabei konnte zunächst der antagonistische Zusammenhang zwischen SOX9 und RUNX2 in CPCs gezeigt werden. Der Knockdown von RUNX2 führte zu einer Hochregulation von SOX9 und damit zu einer Erhöhung des chondrogenen Potentials der Zellen. Umgekehrt führte der Knockdown von SOX9 zu einer Hochregulation von RUNX2 und damit zu einer Verringerung des chondrogenen Potentials der CPCs. Mithilfe massenspektrometrischer Analysen konnten aus Immunpräzipitationen und Pulldown-Isolaten von SOX9 und RUNX2 eine Vielzahl von Proteinen isoliert werden, die mit Signaltransduktionen und der Transkription in Verbindung stehen. Im Rahmen dieser Arbeit wurden einige der möglichen Coaktivatoren von SOX9 in CPCs überexprimiert und mögliche Corepressoren von SOX9 durch siRNA in ihrer Expression inhibiert. Die Überexpression von DDX5, HSPA8, RAB5C und YWHAE führte zu einer Zunahme der Genexpression von SOX9. Während HSPA8 auch eine Zunahme der Genexpression von RUNX2 bewirkte, führte YWHAE zu dessen Herabregulation und damit zu einer Erhöhung des chondrogenen Potentials von CPCs. Durch den Knockdown von LEMD2 und TMPO konnte ebenfalls eine Hochregulation von SOX9 erreicht werden. Ein Anzeichen für die Erhöhung des chondrogenen Potentials bot hierbei zusätzlich die erhöhte Expression der extrazellulären Bestandteile ACAN und die verminderte Expression von COL1A1. Darüber hinaus wurde zum ersten Mal die Interaktion zwischen SOX9 und DDX5 durch Coimmunpräzipitation untersucht. SOX9 konnte dabei copräzipitiert werden allerdings war der umgekehrte und damit der validierende Versuch nicht erfolgreich und bedarf weiterer Untersuchung, z. B. mithilfe einer anderen Methode wie Yeast-Two-Hybrid, um die tatsächliche Protein-Protein-Interaktion zu bestätigen bzw. um sie auszuschließen. Diese Ergebnisse zeigen, dass mithilfe der affnitätschromatographischen Aufreinigung von SOX9 sowie RUNX2 mögliche Interaktionspartner durch massenspektrometrische Analysen der isolierten Proteinkomplexe identifiziert werden können. Inwieweit diese Proteine direkt auf SOX9 einwirken oder Teil einer übergeordneten Transkriptionsmaschinerie sind muss in weiteren Studien untersucht werden, um die Frage zu beantworten, ob diese auch als potentielles Ziel für therapeutische Maßnahmen in Betracht kommen. Darüber hinaus muss die Frage geklärt werden, inwieweit sich die identifizierten Proteine auf die Expression von nachgeschalteten chondrogenen Faktoren auswirken. Diese Arbeiten könnten einen wichtigen Beitrag in der Entwicklung von neuen Therapeutika gegen Osteoarthrose leisten.

Η Οστεοαρθρίτιδα ή αλλιώς η εκφυλιστική νόσος των αρθρώσεων δεν είναι μια μόνο νόσος αλλά μάλλον το τελικό αποτέλεσμα διαφόρων παθήσεων των αρθρώσεων. Σε μεγαλύτερη ή μικρότερη έκταση χαρακτηρίζεται πάντοτε από εκφύλιση του αρθρικού χόνδρου και ταυτόχρονη ανάπτυξη νέου οστού , χόνδρου και συνδετικού ιστού . Η εν λόγω ανάπτυξη έχει ως αποτέλεσμα την αναδιαμόρφωση του περιγράμματος της άρθρωσης . Οι φλεγμονώδεις αλλοιώσεις στην αρθρική μεμβράνη είναι συνήθως μικρές και δευτεροπαθείς . Πρόκειται για μια νόσο η οποία εμφανίζεται στο 80% των ατόμων ηλικίας πάνω από 65 έτη , ως ακτινολογικό εύρημα , ενώ στο 25% αυτών θα παρουσιάζει συμπτώματα . Διάφοροι παράγοντες επηρεάζουν την πορεία της νόσου . Εκτιμάται ότι σε λίγα χρόνια η επίπτωση της νόσου θα είναι τόσο μεγάλη έτσι ώστε δε θα επαρκούν οι ορθοπαιδικοί να χειρουργούν τους ασθενείς !!! Λόγω αυτών επιχειρείται η κατανόηση των μοριακών παθογενετικών μηχανισμών οι οποίοι λαμβάνουν χώρα στην οστεοαρθρίτιδα (ΟΑ) . Ο χόνδρος της άρθρωσης είναι αυτός που εκφυλίζεται με αποτέλεσμα την παραμόρφωση της άρθρωσης . Για την διατήρηση της ακεραιότητας του αρθρικού χόνδρου υπεύθυνη είναι μια λεπτή ισορροπία μεταξύ αναβολικών και καταβολικών διεργασιών που αφορούν τόσο στα χονδροκύτταρα όσο στην εξωκυττάρια θεμέλια ουσία . Η εκφύλιση του εκτελείται από αυξημένη δραστηριότητα των μεταλλοπρωτεασών του στρώματος (Αγκρεκανάσες) καθώς και των υπολοίπων πρωτεολυτικών ενζύμων τα οποία επάγονται από κυτοκίνες ( Il-1 , TNF-a) ή/και προϊόντα αποικοδόμησης της θεμέλιας ουσίας .Αν η εκφύλιση και η καταστροφή του χόνδρου είναι μεγαλύτερη από την παραγωγή νέας θεμέλιας ουσίας από τα χονδροκύτταρα τότε οδηγούμαστε στην ΟΑ . Νέα δεδομένα και απόψεις έρχονται συνεχώς στην επιφάνεια τα οποία υποστηρίζουν την συμμετοχή τόσο του αρθρικού υμένα όσο και του υποχόνδριου οστού στην ανάπτυξη της οστεοαρθρίτιδας . Ο κύριος στόχος αυτής της βιβλιογραφικής εργασίας είναι η λεπτομερής περιγραφή όλων των μορίων και των μονοπατιών που οδηγούν στην ενεργοποίηση των αγγρεκανασών , συνεπώς στην ανάπτυξη της οστεοαρθρίτιδας , την παράθεση των στοιχείων που εμπλέκουν , εκτός του αρθρικού χόνδρου , τον αρθρικό υμένα και το υποχόνδριο οστό στην παθογένεια της , καθώς επίσης τα διάφορα cross talks τα οποία υπάρχουν ανάμεσα στην αναβολική (σύνθεση) και καταβολική (καταστροφή) πορεία του χόνδρου , παρέχοντας έτσι μια καινούρια βάση για μελλοντική ερεύνα και ανακάλυψη νέων φαρμάκων τόσο προληπτικών όσο και θεραπευτικών της οστεοαρθρίτιδας . / -

Knee osteoarthritis (OA) is a progressive disease and a leading cause of morbidity in older adults, resulting in severe mobility limitations. While the osteoligamentous and neuromuscular systems are altered in knee OA, little data is available to illustrate an association among these systems. The objective of this dissertation was to improve our understanding of how muscle activation patterns during gait are altered across the knee OA severity spectrum and to examine how factors related to the OA process are associated with these alterations. Three independent but related studies were conducted. Muscle activation of the medial and lateral orientations of the gastrocnemii, quadriceps and hamstrings were recorded during gait using surface electromyography for all three studies. Key activation features were identified using principal component analysis. First, participants selected from a large group (n=272) of individuals classified as asymptomatic, ii) moderate ii) severe knee OA were matched for walking velocity. Significant amplitude and temporal activation characteristics were found, supporting that differences among OA severities exist and were not the result of walking velocity only. Secondly, individuals with moderate OA were sub-grouped based on structural severity determined using Kellgren-Lawrence radiographic scores (II-IV) and were compared to a velocity-matched asymptomatic group. Medial gastrocnemius, lateral hamstring and quadriceps amplitudes and temporal patterns were significantly altered by structural severity where significant activation imbalances between the lateral:medial gastrocnemii and hamstrings were found with greater structural impairment (score>II). Thirdly, individuals with moderate OA were prospectively evaluated and divided into knee effusion and no effusion groups, based on a positive bulge test. A significantly higher knee flexion angle during mid-stance, higher quadriceps amplitudes and prolonged hamstrings amplitudes were found when effusion was found. These studies showed that muscle activation patterns during walking were related to i) OA presence and severity based on functional, symptoms and radiographic evidence, ii) structural severity and iii) knee joint effusion. These findings improve our understanding of the interrelationships between alterations in joint structure and function associated with knee OA and muscle activation patterns during gait. These data can contribute to the development of gait-based metrics that can facilitate knee OA diagnosis and monitor progression.

This thesis is an investigation of the neurophysiologic mechanism, central sensitization, underlying pain and dysfunction in osteoarthritis. Central sensitization is an important mechanism in the pathophysiology of osteoarthritis but, to our knowledge, its influence on motoneurone excitability is unknown. Our primary hypothesis states that increasing central sensitization within a spinal segment will cause a greater increase in the excitability of motoneurones in subjects with osteoarthritis when compared to healthy controls. To test this hypothesis, we experimentally induced central sensitization in individuals and monitored the recruitment threshold force of the motor units in the first dorsal interosseous muscle using indwelling electromyography. Findings from this study suggest that central sensitization lowers the motor unit recruitment threshold in osteoarthritis compared to healthy individuals. Motoneurone excitability might be inhibited in healthy individuals with persistent sensitization as well. Thus, central sensitization is an important consideration in the biomechanical dysfunction seen in osteoarthritis. / Canadian Arthritis Network

Darbo aktualumas: Osteoartritas (OA) senstančioje visuomenėje darosi vis svarbesnė problema. Daugumai žmonių OA – tai sindromas, kurį sudaro sąnarių skausmo, sustingimo ir dėl to prastėjančių funkcijų simptomai ir kuris daro didelę įtaką gyvenimo kokybei (Conaghan & Sharma, 2009). Sergantiems osteoartritu ligoniams pažeidžiamos daugelis gyvenimo sričių: apsitarnavimas, namų ruoša, darbas, laisvalaikis, judėjimas, miegas (Thorstenson, 2007; Sunden et al. ,2007). Siekiant sumažinti skausmą bei pagerinti funkciją pacientams, sergantiems kelių sąnarių osteoartritu, analizavome, kaip skirtingos kineziterapijos programos veikia pacientų skausmą, pusiausvyrą ir šlaunies raumenų jėgą. Tyrimo objektas: skausmo, pusiausvyros ir raumenų jėgos pokyčiai, taikant skirtingas kineziterapijos programas – kineziterapiją vandenyje bei kelių sąnarių mobilizaciją ir kineziterapiją salėje bei TENS. Tyrimo tikslas: Nustatyti skirtingų kineziterapijos programų efektyvumą ligoniams, sergantiems kelio sąnario osteoartritu. Tyrimo uždaviniai: 1. Nustatyti klinikinio rodiklio – kelių sąnarių skausmo stiprumo – kaitą, taikant skirtingas kineziterapijos programas; 2. Nustatyti funkcinių rodiklių: statinės ir dinaminės pusiausvyros bei blauzdą tiesiančių raumenų jėgos kaitą, taikant skirtingas kineziterapijos programas; 3. Nustatyti, kuri kineziterapijos programa veiksmingesnė, mažinant skausmą ir didinant funkciją – pusiausvyrą bei blauzdą tiesiančių raumenų jėgą. Tyrimo hipotezė: Manome, kad taikydami... [toliau žr. visą tekstą] / Problem of study: Osteoarthritis (OA), in an aging society is becoming increasingly important problem. OA, for the majority of people - is a syndrome consisting of joint pain, stiffness and function because of deteriorating symptoms and who have a significant impact on the quality of life (Conaghan & Sharma, 2009). Patients ill with osteoarthritis are vulnerable to many disabilities in different areas of life: self-service, household chores, work, leisure, movement, sleep (Thorstenson, 2007; Sunden e al. 2007). In order to reduce pain and improve function in patients with knee osteoarthritis, we examined how different physical therapy programes are affecting the pain, balance and strength of the thigh muscles of the patients.. Object of study: changes in pain, balance and muscle strength while applying different physical therapy programs - physical therapy in water, knee joint mobilization, physical therapy room and TENS. Aim of study: to determine the effectiveness of various physical therapy programs for patients with knee osteoarthritis. Goals of study: 1. Establish a clinical indicator – change in the intensity of knee pain with different physical therapy programs; 2. Identify the functional characteristics: static and dynamic balance and change in force of the extensor muscles of the thigh, with different physical therapy programs; 3. To establish which physical therapy program is more effective in reducing pain and improving function - balance and power of the extensor... [to full text]

The progression of knee osteoarthritis (OA), the most common cause of physical disability in older adults, is influenced by muscular and biomechanical factors. Reliability of muscular and biomechanical measures, including knee muscle strength and limb alignment, is critical. Furthermore, conservative interventions that slow the course of OA disease progression and prevent disability are urgently needed. The objectives of this thesis were to: 1) investigate the reliability of measures of knee muscle strength and alignment in persons with knee OA, and 2) determine the influence of an exercise intervention targeting hip muscles on knee joint loading in those with medial knee OA. In the first study reliability of knee muscle strength measures was evaluated within one testing session in 40 persons with knee OA. Isometric and isokinetic peak torque values for the quadriceps and hamstring muscles demonstrated high degrees of intra-session reliability. Reliability of lower limb alignment measures was determined following a bone landmark-based approach with use of a computer program. Excellent reliability coefficients were found which compared favorably with reliability of manual measures from schematics of limb deformities drawn with AutoCAD® software. When the computer method was applied to 100 full-limb radiographs of persons with or at risk for knee OA, alignment measures demonstrated high inter- and intra-reader reliability. Hip muscle weakness may influence loading of the medial knee compartment. Hip abductor strength was evaluated in 40 individuals with medial compartment knee OA in comparison to a control group of 40 healthy older adults. The effect of an 8-week home-based hip abductor strengthening program on the knee adduction moment was also assessed in this group with knee OA, compared with the control group which received no intervention. Following the exercise program the OA group demonstrated improvements in hip abductor strength and functional performance on a sit-to-stand task. There were no changes in the knee adduction moment. Thus, hip muscle strengthening did not influence joint loading, but may improve function in persons with knee OA. Results from this thesis provide increased understanding of knee OA, from muscular and biomechanical perspectives, in the areas of measurement reliability and exercise intervention. / Thesis (Ph.D, Rehabilitation Science) -- Queen's University, 2008-09-25 01:29:13.675

No description available.

Osteoarthritis (OA) is a group of diseases entailing degradation of joints, and has been designated as one of the key conditions for special attention during the World Health Organization’s Bone and Joint Decade (2000-2010) (Brooks & Hart, 2000). Research has demonstrated that body weight is the number one modifiable risk factor associated with the onset and progression of knee OA (Felson, 1996). However, exercise programs that aim to initiate weight loss and improve pain and function in knee OA often increase loading on the knee joint, contributing to degeneration of the knee and progression of the disease (Miyazaki et al, 2002). The introduction of a new anti-gravity treadmill, which utilizes a technology called Lower Body Positive Pressure (LBPP), allows the examination of the relationship between weight, knee pain and knee loading via knee acceleration during exercise. The null hypothesis states that there will be no significant difference in knee pain, knee function and knee joint acceleration when comparing full weight bearing and LBPP treadmill walking exercise in a young knee OA population. Twenty-two overweight/obese patients with mild or moderate early-onset knee OA were recruited to complete two 25 minute treadmill walking sessions (one full weight-bearing and one LBPP walking session) one week apart and two walkway walking sessions. Knee pain and knee acceleration were recorded. Paired t-tests and ANOVAs were used to compare conditions. On average, an LBPP of 12.3% body weight reduction reduced knee pain in our population. Knee pain was significantly lower during LBPP walking than during full weight-bearing walking. Knee acceleration decreased with increasing LBPP. Heel strike and toe-off data from walkway walking trials illustrated significantly different knee acceleration about the knee (slow walking loads were lower / fast walking were higher), as compared to treadmill walking sessions. This study illustrates that treadmill walking at a minimal level of LBPP can decrease knee pain and attenuate knee joint loads while allowing patients to complete exercise programs aimed at initiating weight loss and improving pain and function in knee OA. LBPP appears to be a promising tool for rehabilitation for those with painful knee OA and other lower body musculoskeletal conditions.

Knee osteoarthritis (OA) is a degenerative joint condition characterized by progressive joint pain, swelling, and loss of muscle and joint function for which there is no known cure. Current research indicates that the most important modifiable risk factor for the development and progression of knee OA is obesity, a condition that is increasingly common in older adults. Established treatment guidelines for knee OA recommend regular exercise for disease management. However, for obese patients weight-bearing exercise elicits large joint forces that can exacerbate symptoms and influence disease progression. Using a new anti-gravity treadmill capable of generating a lifting force called lower body positive pressure (LBPP), obese patients with knee OA can engage in regular physical activity while minimizing joint loading. The aim of this study was to assess the effect of a 12-week, anti-gravity treadmill walking (AGTW) program on knee pain and function in obese older adults with knee OA. The alternate hypothesis was that there would be a difference between Knee Injury and Osteoarthritis Outcome Score (KOOS) results before and after the anti-gravity treadmill walking program. A group of 25 participants with a mean (SD) age of 64.2 (6.1) years and BMI of 33.0 (6.8) kg/m2 completed AGTW twice per week for 12 weeks at a body weight percentage that minimized knee pain. Knee symptoms and function (KOOS), knee pain during full weight-bearing treadmill walking (FTW), isokinetic quadriceps and hamstring muscle strength, cardiovascular fitness (YMCA submaximal cycle ergometer test), general health status (SF-12), and activity level (average daily pedometer readings) were assessed at baseline and following the completion of the 12-week program using paired t-tests and Wilcoxon signed rank sum tests (α = 0.05). Improvements between baseline and outtake were found in all KOOS subscales, as well as hamstring and quadriceps thigh muscle strength. Knee pain during full FWB and AGTW decreased following the 12-week program. No significant differences were found in cardiovascular fitness, SF-12 scores, or average daily pedometer readings. The results of this study suggest that anti-gravity treadmill walking increases thigh muscle strength, reduces knee pain, and increases functional capacity during daily activities, including FTW in older, obese individuals with knee OA. Anti-gravity treadmill technology has the potential to improve the health and functional capacity of at-risk knee OA individuals, and advance current methods of rehabilitation and long-term management of chronic symptomatic knee OA.

No description available.