La compréhension de la biomécanique des structures articulaires est inhérente à l'amélioration de l'évaluation clinique de l'articulation coxo-fémorale. Cette articulation possède une capsule articulaire qui contient du liquide synovial et composée de ligaments capsulaires. Premièrement, le volume du liquide synovial peut être modifié en présence d'un problème articulaire. La pression intracapsulaire sera donc modifiée par ce changement de volume et par les mouvements articulaires effectués. Deuxièmement, les ligaments capsulaires s’allongent en fonction des différentes amplitudes articulaires. Les six degrés de liberté de mouvement de l'articulation coxo-fémorale rendent plus complexes l'évaluation et l'interprétation des pressions intracapsulaires et des allongements ligamentaires. À ce jour, les informations sur les pressions intracapsulaires et les allongements ligamentaires pendant les mouvements de l'articulation sont incomplètes ou limitées. La première étude visait à présenter les fluctuations des pressions intracapsulaires lors de cinq mouvements classiques au sein des compartiments capsulaire (latéral) et acétabulaire (médial). Latéralement, la pression est liée à l’amplitude articulaire. Médialement, la pression est beaucoup plus réactive aux mouvements. Cette première étude montre une variabilité importante entre les mouvements et les compartiments dans lesquels la pression est évaluée. La deuxième étude visait à rapporter les pressions dans les tests de provocation de flexion-abduction-rotation externe (FABER) et de flexion-adduction-rotation interne (FADIR). Lors du test de FABER, la pression intracapsulaire est négative dans les deux compartiments capsulaires. Pour le test de FADIR, la pression intracapsulaire est très élevée dans le compartiment latéral. Cette augmentation significative pourrait présenter une explication des problèmes de sensibilité et de spécificité du test de FADIR face à des modifications ostéologiques qui sont habituellement évaluées lors de son exécution. La troisième étude visait à présenter les allongements longitudinaux et transversaux du ligament iliofémoral lors de quatre mouvements articulaires soient l’abduction, la rotation externe et interne en extension et l’extension seule. Nos résultats montrent une hétérogénéité importante au sein des deux faisceaux du ligament iliofémoral lors de ces mouvements articulaires. La quatrième étude portait sur les allongements ligamentaires au sein du ligament iliofémoral lors du test de FABER. D’après nos résultats, il est possible d’observer des allongements significativement différents entre les faisceaux médial et latéral du ligament iliofémoral. Le faisceau latéral s’allonge dans sa globalité. L’allongement le plus important est observé dans la portion distale de ce faisceau. Médialement, le faisceau rétrécissait. Au regard de ces différents résultats entre les deux faisceaux, une distinction est nécessaire lors du test de FABER. En fait, ils auront des comportements complètement différents. En conclusion, ces quatre études portent sur l’analyse des pressions intracapsulaires et des allongements ligamentaires lors des mouvements classiques et des tests de provocation. Les différentes études montrent que la pression est dépendante du mouvement et du compartiment dans lequel elle est évaluée. Quant aux allongements, ceux-ci varient en regard du mouvement, de la portion et du faisceau dans lesquels ils sont évalués. Ces résultats soulignent l’importance de prendre en considération ces variations lors de l’évaluation clinique de la hanche. / Understanding tissue and joint biomechanics are inherent to improving the clinical evaluation of the coxofemoral joint. The coxofemoral joint has a joint capsule that contains synovial fluid and is composed of capsular ligaments. Firstly, the volume of synovial fluid can increase in the presence of a joint problem. The intra-articular pressure will therefore be modified by this change in volume and by the joint movements performed. Secondly, the capsular ligaments increase or decrease in length depending on the movement performed. The six degrees of freedom of movement of the coxofemoral joint make the assessment and interpretation of intra-articular pressures and ligament strains more complex. To date, information on intra-articular pressure and ligament strains during joint range of motion are incomplete or limited. The first study intended to present the fluctuations of intra-articular pressures during five classical movements within the capsular (lateral) and acetabular (medial) compartments. Laterally, the pressure is related to joint range of motion. Medially, the pressure is much more reactive. This study shows significant variability between movements and compartments in which the pressure is assessed. The second study aimed to report pressures in the flexion-abduction-external rotation (FABER) and flexion-adduction-internal rotation (FADIR) provocation tests. In the FABER test, the intra-articular pressure was negative in both capsular compartments. For the FADIR test, the intra-articular pressure was very high in the lateral compartment. This significant increase could present an explanation for the sensitivity and specificity problems of the FADIR test in the face of osteological changes. The third study aimed to present the longitudinal and transverse strains of the iliofemoral ligament during four joint movements, namely abduction, external and internal rotation in extension and extension alone. Our results show significant heterogenity within the two bands of the iliofemoral ligament during these joint movements. The fourth study looked at ligament strains within the iliofemoral ligament during the FABER test. According to our results, it is possible to observe significantly different strains between the medial and lateral bands of the iliofemoral ligament. The lateral band increase in length globally. The largest strain was observed in the distal portion of this band. Medially, the band decreases in length. In view of these different results between the two bands, it is important to distinguish them when performing the FABER test as they will have completely different behaviors. In conclusion, these four studies describe the analysis of intra-articular pressures and ligament strains during the classical movement and provocation test. They show that the pressure is dependent on the movement and the compartment in which it is assessed. As for ligament strains, they vary according to the movement, the portion, and the band in which they are evaluated. These results underline the importance of taking these variations into consideration during the clinical evaluation of the hip.

Realizamos estudo prospectivo randomizado para comparar cinco métodos específicos de avaliação funcional do ombro e uma avaliação genérica da saúde em pacientes operados de capsuloplastia e descompressão subacromial associado à reparação do manguito rotador. Foram estudados 30 pacientes de cada grupo, avaliados no período entre cinco a seis meses após o tratamento cirúrgico com os questionários dos Cirurgiões Americanos de Ombro e Cotovelo(ASES), Sistema de Pontuação do Ombro de Constant & Murley (CONSTANT), Folha de Classificação da Reparação de Bankart (ROWE), Teste Simples de Ombro (SST), Escala de Avaliação do Ombro da Universidade de Califórnia - Los Angeles (UCLA) e o Questionário Genérico de Avaliação de Qualidade de Vida (SF-36). A idade no grupo de \"Descompressão\" variou de 44 a 77 anos (média 59,2) e no grupo de \"Capsuloplastia\" foi de 17 a 65 anos (média de 31,4). Em relação ao sexo, o grupo da \"Descompressão\" foi predominantemente feminino e no grupo da \"Capsuloplastia\" foi predominante o sexo masculino. As médias da pontuação no grupo de \"Capsuloplastia\" são maiores que no \"Descompressão\" (93,6 e 71,7 respectivamente). A variabilidade dos escores observado no grupo \"Capsuloplastia\" (89,1 a 100) é inferior ao do grupo \"Descompressão\" (65,1 a 95,9). Não existe uma forte concordância entre os resultados obtidos pelos diferentes questionários (variação de zero a 0,51). A média nos oito domínios do SF-36 no grupo \"Descompressão\" foi de 70,8 variando de 60,4 (Vitalidade) a 89,2 (Aspectos Sociais). Para o grupo \"Capsuloplastia\" a média foi de 91,2 variando de 83,4 (Saúde Mental) a 96,6 (Aspectos Emocionais). Nos coeficientes de correlação linear de Pearson, não foi detectada associação linear entre a escala de CONSTANT e SF-36 no grupo \"Descompressão\" e entre ROWE e SF-36 no grupo \"Capsuloplastia\". Em ambos os grupos a maior correlação encontrada foi entre os questionários UCLA e ASES (0,900 na \"Descompressão\" e 0,893 na \"Capsuloplastia\"). Concluiu-se que nas cirurgias de descompressão subacromial o questionário UCLA foi o mais completo mostrando maior confiabilidade e reprodutibilidade e para as capsuloplastias o método ROWE apresentou maior confiabilidade, reprodutibilidade e praticidade. / A prospective randomized study was realized to compare methods of both disease specific and generic health status of shoulder\'s functional assessment in patients after operative treatment of subacromial decompression associated a repair of a tear of the rotator cuff and capsuloplasty. The thirty patients in each group were studied and at follow-up five to six months later, with the following questionnaires: American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES), Constant-Murley Shoulder Scoring System (CONSTANT), Rating Sheet for Bankart Repair (ROWE), Simple Shoulder Test (SST), University of California at Los Angeles Shoulder Rating Scale (UCLA) and the Short Form-36 (SF-36). The age in Decompression group was greater than Capsuloplasty group and the gender of first group was predominantly consisted of women and in the second group was men. The scores averages of Capsuloplasty group were higher than Decompression group (93,6 and 71,7 respectively). The variability of the scores observed in the Capsuloplasty group, 89,1 to 100,0 was less than in the Decompression group, 65,1 to 95,9. A strong interrater reliability between the questionnaires does not exist - variation 0 to 0,51. The average in the eight domains of SF-36 in Decompression group was 70,8 [range 60,4 (Vitality) to 89,2 (Social Aspect)]. In Capsuloplasty group the average was 91,2 [range 83,4 (Mental Health) to 96,6 (Emotional Aspect) ]. Pearson\'s coefficient analysis, shows that the correlation between CONSTANT and SF-36 was not detect, and in Capsuloplasty was not detect in ROWE and SF-36. In both groups Capsuloplasty (0,893) and Decompression (0,900), a strong correlation between UCLA and ASES were observed. It follows that to subacromial decompression surgery, UCLA shows more reliability and in Capsuloplasty, the Rowe method shows more applicability.

Realizamos estudo prospectivo randomizado para comparar cinco métodos específicos de avaliação funcional do ombro e uma avaliação genérica da saúde em pacientes operados de capsuloplastia e descompressão subacromial associado à reparação do manguito rotador. Foram estudados 30 pacientes de cada grupo, avaliados no período entre cinco a seis meses após o tratamento cirúrgico com os questionários dos Cirurgiões Americanos de Ombro e Cotovelo(ASES), Sistema de Pontuação do Ombro de Constant & Murley (CONSTANT), Folha de Classificação da Reparação de Bankart (ROWE), Teste Simples de Ombro (SST), Escala de Avaliação do Ombro da Universidade de Califórnia - Los Angeles (UCLA) e o Questionário Genérico de Avaliação de Qualidade de Vida (SF-36). A idade no grupo de \"Descompressão\" variou de 44 a 77 anos (média 59,2) e no grupo de \"Capsuloplastia\" foi de 17 a 65 anos (média de 31,4). Em relação ao sexo, o grupo da \"Descompressão\" foi predominantemente feminino e no grupo da \"Capsuloplastia\" foi predominante o sexo masculino. As médias da pontuação no grupo de \"Capsuloplastia\" são maiores que no \"Descompressão\" (93,6 e 71,7 respectivamente). A variabilidade dos escores observado no grupo \"Capsuloplastia\" (89,1 a 100) é inferior ao do grupo \"Descompressão\" (65,1 a 95,9). Não existe uma forte concordância entre os resultados obtidos pelos diferentes questionários (variação de zero a 0,51). A média nos oito domínios do SF-36 no grupo \"Descompressão\" foi de 70,8 variando de 60,4 (Vitalidade) a 89,2 (Aspectos Sociais). Para o grupo \"Capsuloplastia\" a média foi de 91,2 variando de 83,4 (Saúde Mental) a 96,6 (Aspectos Emocionais). Nos coeficientes de correlação linear de Pearson, não foi detectada associação linear entre a escala de CONSTANT e SF-36 no grupo \"Descompressão\" e entre ROWE e SF-36 no grupo \"Capsuloplastia\". Em ambos os grupos a maior correlação encontrada foi entre os questionários UCLA e ASES (0,900 na \"Descompressão\" e 0,893 na \"Capsuloplastia\"). Concluiu-se que nas cirurgias de descompressão subacromial o questionário UCLA foi o mais completo mostrando maior confiabilidade e reprodutibilidade e para as capsuloplastias o método ROWE apresentou maior confiabilidade, reprodutibilidade e praticidade. / A prospective randomized study was realized to compare methods of both disease specific and generic health status of shoulder\'s functional assessment in patients after operative treatment of subacromial decompression associated a repair of a tear of the rotator cuff and capsuloplasty. The thirty patients in each group were studied and at follow-up five to six months later, with the following questionnaires: American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES), Constant-Murley Shoulder Scoring System (CONSTANT), Rating Sheet for Bankart Repair (ROWE), Simple Shoulder Test (SST), University of California at Los Angeles Shoulder Rating Scale (UCLA) and the Short Form-36 (SF-36). The age in Decompression group was greater than Capsuloplasty group and the gender of first group was predominantly consisted of women and in the second group was men. The scores averages of Capsuloplasty group were higher than Decompression group (93,6 and 71,7 respectively). The variability of the scores observed in the Capsuloplasty group, 89,1 to 100,0 was less than in the Decompression group, 65,1 to 95,9. A strong interrater reliability between the questionnaires does not exist - variation 0 to 0,51. The average in the eight domains of SF-36 in Decompression group was 70,8 [range 60,4 (Vitality) to 89,2 (Social Aspect)]. In Capsuloplasty group the average was 91,2 [range 83,4 (Mental Health) to 96,6 (Emotional Aspect) ]. Pearson\'s coefficient analysis, shows that the correlation between CONSTANT and SF-36 was not detect, and in Capsuloplasty was not detect in ROWE and SF-36. In both groups Capsuloplasty (0,893) and Decompression (0,900), a strong correlation between UCLA and ASES were observed. It follows that to subacromial decompression surgery, UCLA shows more reliability and in Capsuloplasty, the Rowe method shows more applicability.

Articular cartilage is an avascular and flexible connective tissue found in joints. It produces a cushioning effect at the joints and provides low friction to protect the ends of the bones from wear and tear/damage. It has poor repair capacity and any injury can result pain and loss of mobility. One of the common forms of articular cartilage disease which has a huge impact on patient's life is arthritis. Research on cartilage cell/tissue engineering will help patients to improve their physical activity by replacing or treating the diseased/damaged cartilage tissue. Cartilage cell, called chondrocyte is embedded in the matrix (Lacunae) and has round shape in vivo. The in vitro monolayer culture of primary chondrocyte causes morphological change characterized as dedifferentiation. Transforming growth factor-beta (TGF-β), a cytokine superfamily, regulates cell function, including differentiation and proliferation. The effect of TGF-β1, 2, 3, and their manipulated forms in biological regulation of primary chondrocyte was investigated in this work. A novel method was developed to isolate and purify the primary chondrocytes from knee joint of neonate Sprague-Dawley rat, and the effect of some supplementations such as hyaluronic acid and antibiotics were also investigated to provide the most appropriate condition for in vitro culture of chondrocyte cells. Addition of 0.1mg/ml hyaluronic acid in chondrocyte culture media resulted an increase in primary chondrocyte proliferation and helped the cells to maintain chondrocytic morphology. TGF-β1, 2 and 3 caused chondrocytes to obtain fibroblastic phenotype, alongside an increase in apoptosis. The healing process of the wound closure assay of chondrocyte monolayers were slowed down by all three isoforms of TGF-β. All three types of TGF-β negatively affected the strength of chondrocyte adhesion. TGF-β1, 2 and 3 up regulated the expression of collagen type-II, but decreased synthesis of collagen type-I, Chondroitin sulfate glycoprotein, and laminin. They did not show any significant change in production of S-100 protein and fibronectin. TGF-β2, and 3 did not change expression of integrin-β1 (CD29), but TGF-β1 decreased the secretion of this adhesion protein. Manipulated TGF-β showed huge impact on formation of fibroblast like morphology of chondrocytes with chondrocytic phenotype. These isoforms also decreased the expression of laminin, chondroitin sulfate glycoprotein, and collagen type-I, but they increased production of collagen type-II and did not induce synthesis of fibronectin and S-100 protein. In addition, the strength of cell adhesion on solid surface was reduced by manipulated TGF-β. Only manipulated form of TGF-β1 and 2 could increase the proliferation rate. Manipulation of TGF-β did not up regulate the expression of integrin-β1 in planar culture system. The implications of this R&D work are that the manipulation of TGF-β by combination of TGF-β1, 2, and 3 can be utilized in production of superficial zone of cartilage and perichondrium. The collagen, fibronectin and hyaluronic acid could be recruited for the fabrication of a biodegradable scaffold that promotes chondrocyte growth for autologous chondrocyte implantation or for formation of cartilage.

<p>Uvod: magnetno rezonantni imidžing (MR) je u &scaron;irokoj uporebi u dijagnostici patolo&scaron;kih poremećaja ekstremiteta. Postoji interes da se redukuje vreme trajanja snimanja tokom pregleda kako bi se povećao komfor pacijenata i redukovali problemi koji su u vezi sa klaustrofobijom i artefaktima koji nastaju pri pomeranju pacijenta tokom dugih snimanja. Trodimenzionalne (3D) izovoksel sekvence pokazale su značajne mogućnosti u redukciji vremena snimanja MR pregledom zgloba kolena bez smanjenja kvaliteta dijagnostičkih mogućnosti. Cilj: uporediti dijagnostičke mogućnosti rutinskog, 2D MR protokola, na 3.0 Tesla MR aparatu, sa 3D True fast imaging, TrueFISP, izovoksel sekvencom u detekciji hondralnih o&scaron;tećenja, ruptura prednjeg ukr&scaron;tenog ligamenta (LCA), ruptura meniskusa i abnormalnosti subhondralne kosti, u korelaciji sa artroskopijom, kao referentnim standardom. Materijal i metode: Studija je odobrena od institucionalnog etičkog odbora. Pacijenti su informisani o studiji i potpisali pristanak za uče&scaron;će u istraživanju. 76 zgloba kolena kod 76 pacijenata (34 ženskog pola; prosečne starosti 36 godina) uključeno je u prospektivnu studiju, snimljeno je standardnim 2D MR protokolom snimanja i 3D TrueFISP sekvencom u sagitalnoj ravni. Svim pacijentima je urađena artroskopija u periodu od maksimum 30 dana nakon snimanja. Dva radiologa, nezavisno jedan od drugog, su evaluirala dobijene snimke. Preciznost u detekciji hondralnih o&scaron;tećenja, ruptura LCA i meniskusa, i abnormalnosti subhondralne kostne srži je određena podudarno&scaron;ću radiolo&scaron;kih i artroskopskih nalaza kao i proverom podudaranja ove dve metode snimanja. Rezultati: prosečna senzitivnost i specifičnost 3DTrueFISP sekvence je bila 75%, 94% respektivno, u dijagnostici o&scaron;tećenja hrskavice, 97%, 97% u detekciji ruptura LCA, 65%, 89% u postavljanju dijagnoze ruptura meniskusa, a dobra podudarnost radiolo&scaron;kih nalaza je dobijena u interpretaciji o&scaron;tećenja subhondralne kosti. Standardnim 2D MR protokolom prosečna senzitivnost i specifičnost je bila 70%, 93%, respektivno, u postavljanju dijagnoze hondralnih o&scaron;tećenja, 94% i 100% u postavljanju dijagnoze rupture LCA, 65%, 88% u detekciji ruptura meniskusa. Zaključak: dijagnostičke mogućnosti upotrebom 3DTrueFISP sekvence su uporedive sa standardnim, 2D, MR protokolom u snimanju zgloba kolena.</p> / <p>Introduction: Magnetic resonance imaging (MR) is widely used to assess internal derangements of the extremities. There is an interest in decreasing examination times to improve patient comfort and reduce the problems related to claustrophobia and motion artifacts, which occur more commonly with long examinations. The three-dimensional (3D) isovoxel true FISP sequence facilitates a noticeable reduction in acquisition time for MR imaging of the knee without reducing diagnostic performance. Objective: To compare the diagnostic performance of conventional, 2D, MR protocol, at 3.0 Tesla MR, with 3D water-excitation true fast imaging with steady-state precession, TrueFISP, an isotropic resolution sequence for detecting articular cartilage defects, anterior crucial ligament tears, meniscal tears and subhondral bone changes of the knee joint, with arthroscopy as reference standard. Materials and methods: The study was institutional review board approved. Written informed consent was obtained from all patients. 76 knees of 76 patients (34 females; mean age 36 years) were prospectively examined by using a conventional 2D MR protocol and sagittal 3D TrueFISP sequence. All patients underwent arthroscopy within a maximum period of 30 days after imaging. Two blinded readers evaluated the MR images. Accuracy for detection of cartilage defects, anterior cruciate ligament and meniscal tears, and subchondral bone abnormalities interobserver agreement, and intermethod agreement were calculated. Results: Overall sensitivity and specificity of 3DTrueFISP sequence were, respectively, 75%, 94% for diagnosis cartilage defects, 97%, 97%, for a diagnosis ACL tears, 65%, 89% for diagnosis of meniscal tears and with good interobserver agreement in interpretation of subhondral bone abnormalities. The standard MR protocol had overall sensitivities and specificities 70%, 93%, respectively, for diagnosis of cartilage defects, 94% and 100% for diagnosis ACL tears and 65%, 88% for diagnosis meniscal tears. Conclusion: The diagnostic perfomance of knee MR imaging performed by using a 3DTrueFISP sequence is comparable to the diagnostic performance of the conventional, 2D, MR protocol.</p>

Le développement et l'homéostasie des os requièrent l'orchestration spatio-temporelle d'un grand nombre de signaux moléculaires. Ces signaux entraînent l'activation ou l'inhibition de différents facteurs de transcription, lesquels sont en mesure de contrôler la prolifération et la différenciation des ostéoblastes et des chondrocytes. L'intégrité de ces différents mécanismes se doit d'être maintenu tout au long de la vie. Ainsi, une anomalie dans l'un de ces mécanismes conduit à l'apparition de pathologies osseuses et métaboliques telles qu’une hypophosphatémie, l'ostéoporose ou l'ostéoarthrite (OA). Afin d'en apprendre davantage sur la biologie osseuse, le projet décrit dans cette thèse a pour objectif de caractériser de nouveaux mécanismes de régulation transcriptionnelle pour deux gènes importants dans le développement des os et le maintien de leur intégrité. Il s’agit du Paired-like Homeodomain Transcription Factor 1 (PITX1) et du Phosphate-regulating gene with homology to endopeptidase on the X chromosome (PHEX). Le premier mécanisme présenté dans cette thèse concerne la régulation transcriptionnelle du gène PITX1, un facteur de transcription à homéodomaine nécessaire, notamment, au développement des os des membres inférieurs et au maintien de l'intégrité du cartilage articulaire chez l'adulte. Ainsi, dans les chondrocytes articulaires, on note que l'expression de PITX1 est assurée par le recrutement du facteur de transcription E2F1 à deux éléments de réponse présents dans la région proximale du promoteur de PITX1. Aussi, dans les chondrocytes articulaires de patients souffrant d'OA, dans lesquels l'expression de PITX1 est fortement diminuée, un mécanisme de répression transcriptionnelle, lequel implique la protéine multifonctionnelle Prohibitin (PHB1), semble être activé. En effet, dans ces chondroytes, on note une forte accumulation nucléaire de PHB1 comparativement aux chondrocytes articulaires de sujets sains. Le second mécanisme présenté dans cette thèse concerne la répression transcriptionnelle de PHEX, la peptidase mutée dans le syndrome d'hypophosphatémie lié au chromosome X (X-Linked Hypophosphatemia, XLH), lequel se caractérise par une hypophosphatémie et une ostéomalacie. Le traitement d'ostéoblastes à la Parathyroid hormone-related protein (PTHrP) permet d’observer la répression de PHEX. Afin de caractériser le mécanisme responsable de cette répression, des expériences de gènes rapporteurs ont révélé la présence de deux éléments de réponse pour le répresseur transcriptionnel E4BP4 dans le promoteur de PHEX. La suppression de l'expression d'E4BP4 par l'utilisation d'ARN d'interférence a permis de valider que ce facteur de transcription est responsable de la répression de PHEX suite au traitement d'ostéoblastes à la PTHrP. En somme ces nouveaux mécanismes de régulation transcriptionnelle permettent de mieux comprendre la régulation de l'expression de PITX1 et de PHEX. Aussi, cette nouvelle implication de PHB1 dans la pathogenèse de l'OA offre de nouvelles possibilités de traitement et pourrait servir pour le diagnostic précoce de cette pathologie. Enfin, la caractérisation d'E4BP4 en tant que médiateur pour la répression de PHEX par la PTHrP suggère que ce répresseur transcriptionnel pourrait être impliqué dans le contrôle de la minéralisation des os et des niveaux de phosphate sanguin. / Bone development and homeostasis need a large amount of molecular signals to be finely regulated in time and space. These signals lead to the activation or to the inhibition of different transcription factors, which are implicated in the control of osteoblast and chondrocyte proliferation and differentiation. The integrity of these mechanisms is required in order to have a healthy life. Indeed, if one of these mechanisms is dysfunctional, different diseases could develop such as hypophosphatemia, osteoporosis and osteoarthritis (OA). In order to contribute to the comprehension of bone biology, the present thesis describes new mechanisms for the transcriptional regulation of two genes implicated in bone development and regulation: PITX1 (Paired-like Homeodomain Transcription Factor 1) and PHEX (Phosphate-regulating gene with homology to endopeptidase on the X chromosome). The first mechanism described in this thesis relates to the transcriptional regulation of PITX1, a gene that encodes for a member of the homeobox family of transcription factors. PITX1 is required in bone development of inferior members and in the maintenance of the articular cartilage integrity in adults. Thereby, we showed that in articular chondrocytes, the expression of PITX1 is activated after the transcription factor E2F1 was recruited at two response elements in the proximal region of its promoter. Moreover, in articular chondrocytes from OA patients, we observed that the expression of PITX1 is strongly decreased. We proposed that the mechanism responsible for this repression requires the multitask protein Prohibitin (PHB1), which is strongly accumulated in OA chondrocyte nuclei, but not in chondrocyte nuclei from healthy individuals. The second mechanism described in this thesis reports a transcriptional mechanism by which PHEX, the gene that encodes for the peptidase mutated in the syndrome X-Linked Hypophosphatemia (XLH)and characterized by hypophosphatemia and osteomalecia, is repressed. We showed that the treatment of osteoblasts with the Parathyroid hormone-related protein (PTHrP) induced a decrease in PHEX expression. In order to characterize the mechanism responsible for this repression, we performed gene reporter experiments and identified two response elements for the transcription factor E4BP4 in the PHEX promoter. The downregulation of E4BP4 by siRNA led to the validation that this repressor decreased the expression of PHEX in osteoblasts after their treatment with PTHrP. In conclusion, the new transcriptional mechanisms presented in this thesis allow a better understanding of PITX1 and PHEX expression. Moreover, the potential role of PHB1 in the establishment of OA presents many interesting possibilities regarding the treatment and diagnosis of this disease. Finally, the characterization of E4BP4 as a mediator of PHEX repression by the PTHrP suggests that E4BP4 could be implicated in the control of bone mineralization and phosphate levels in the blood.

La structure du cartilage articulaire adulte est caractérisée par la présence de couches créées par l’orientation des fibres de collagène (Benninghoff, 1925). Avant de présenter la structure adulte classique en arcades “de Benninghoff”, le cartilage subit une série de changements au cours de sa maturation (Julkunen et al., 2010; Lecocq et al., 2008). Toutefois, un faible nombre d’études s’est intéressé à la structure du collagène du cartilage articulaire in utero. Notre objectif était d’étudier la maturation de la surface articulaire de l’épiphyse fémorale distale chez le cheval, en employant à la fois l’imagerie par résonance magnétique (IRM) et la microscopie en lumière polarisée après coloration au rouge picrosirius, au niveau de sites utilisés dans les études de réparation tissulaire et de sites prédisposés à l’ostéochondrose (OC). Le but était de décrire le développement normal du réseau de collagène et la relation entre les images IRM et la structure histologique. Des sections provenant de cinq sites de l’épiphyse fémorale distale de 14 fœtus et 10 poulains et adultes ont été colorées au rouge picrosirius, après que le grasset ait été imagé par IRM, dans l’optique de visualiser l’agencement des fibres de collagène de type II. Les deux modalités utilisées, IRM et microscopie en lumière polarisée, ont démontré la mise en place progressive d’une structure en couches du réseau de collagène, avant la naissance et la mise en charge de l’articulation. / Adult articular cartilage has a zonal or layered structure, created by the predominant collagen fibre orientation (Benninghoff, 1925). Before reaching the classical “Benninghoff structure”, major changes take place with maturation from juvenile to adult cartilage (Julkunen et al., 2010; Lecocq et al., 2008). However, there have been few studies addressing the in utero collagen structure of articular cartilage. Our objective was to study the maturation of the distal femoral epiphysis articular surface, employing both magnetic resonance imaging and polarized light microscopy with picrosirius red staining, at sites employed for cartilage repair studies or susceptible to osteochondrosis to describe normal development of the spatial architecture of the collagen network at these sites and the relationship between magnetic resonance images and histology. Samples were harvested from five sites from the distal femoral epiphysis of 14 fetuses and 10 foals and adults, after the stifle was imaged with magnetic resonance imaging. Sections were stained with picrosirius red to determine the structural arrangement of the type II collagen fibres. Both magnetic resonance imaging and polarized light microscopy revealed an early progressive structural laminar/zonal organization of the collagen network, prior to birth and postnatal load-bearing.

INTRODUÇÃO: Pacientes com rigidez pós-traumática do cotovelo que falharam à fisioterapia convencional têm como possibilidades de tratamento protocolos de reabilitação associado ao uso de órtese ou à liberação cirúrgica do cotovelo. Na literatura não existem artigos comparativos entre essas duas formas de tratamento. O objetivo primário deste estudo foi comparar a amplitude de movimento de flexoextensão do cotovelo entre os pacientes submetidos ao tratamento cirúrgico ou à reabilitação. Os objetivos secundários foram comparar os resultados clínicos, de acordo com a escala \"Mayo Elbow Performance Score\", o questionário \"Disability of Arm, Shoulder and Hand\" e a escala visual analógica de dor, além de comparar o ganho absoluto e relativo da flexoextensão, a flexão e extensão máxima, a amplitude de pronossupinação e a taxa de complicações. MÉTODOS: Estudo clínico randomizado, com avaliador cego, de pacientes com rigidez póstraumática do cotovelo que apresentaram falha ao tratamento fisioterápico convencional. Os pacientes foram alocados aleatoriamente em dois grupos de tratamento: conservador e cirúrgico. O grupo conservador foi submetido ao protocolo de reabilitação envolvendo a equipe de terapia ocupacional, com exercícios e alongamentos associados ao uso de órteses estáticas seriadas de extensão, dinâmicas de flexão, além de sessões de movimentação contínua passiva. O grupo cirúrgico foi submetido à liberação cirúrgica por via posterior, seguido do mesmo protocolo de reabilitação do grupo conservador. As escalas clínicas foram aplicadas pré-operatoriamente, aos 3 e 6 meses de seguimento. A amplitude de movimento foi avaliada nos mesmos períodos e adicionalmente com 6 semanas. As complicações foram avaliadas até os 6 meses de tratamento. O desfecho primário do estudo foi a amplitude de movimento de flexoextensão aos 6 meses de seguimento. RESULTADOS: Trinta pacientes foram incluídos no estudo, sendo 15 em cada grupo. A amplitude de movimento de flexoextensão do cotovelo, ao final dos 6 meses de seguimento, foi de 108,4º para o grupo cirúrgico e de 88,1º para o grupo conservador (p=0,002). O ganho absoluto e relativo da flexoextensão do cotovelo aos 6 meses foram respectivamente de 17,2º e 26,8% para o grupo conservador e de 40,8º e 58,8% para o grupo cirúrgico (p < 0,001). A pontuação da escala visual analógica de dor, escala \"Mayo Elbow Performance Score\" e o questionário \"Disability of Arm, Shoulder and Hand\" foram respectivamente de 4,4, 70,6 e 35,3 para o grupo conservador e de 3,9, 77,3 e 27,6 para o grupo cirúrgico (p=0,486, p=0,342 e p=0,361). O grupo conservador apresentou uma complicação, enquanto o grupo cirúrgico quatro (p=0,598). CONCLUSÕES: A liberação cirúrgica do cotovelo associada ao protocolo de reabilitação resultou em uma maior amplitude de flexoextensão, além de um maior ganho absoluto e relativo quando comparada à reabilitação isolada após 6 meses. A extensão máxima obtida foi superior no grupo cirúrgico, sem diferença para a flexão máxima e amplitude de movimento de pronossupinação. Os grupos não diferiram nas escalas funcionais e na taxa de complicações / INTRODUCTION: Patients with post-traumatic elbow stiffness who have failed conventional physiotherapy have two options of treatment: rehabilitation protocols associated with the use of bracing or surgical elbow release. In the literature there are no comparative studies between those forms of treatment. The primary objective of this study was to compare the elbow flexion-extension range of motion between patients submitted to surgical treatment or rehabilitation. The secondary objectives were to compare the clinical outcomes according to the Mayo Elbow Performance Score, the Disability of Arm, Shoulder and Hand questionnaire and the visual analogue pain scale, in addition to comparing the absolute and relative gain of elbow flexion-extension, maximal flexion and extension, pronosupination range of motion and complications rate. METHODS: Randomized clinical trial with blind evaluator of patients with post-traumatic elbow stiffness who presented failure to conventional physiotherapeutic treatment. Patients were randomly assigned to two treatment groups: non surgical and surgical. The non surgical group was submitted to a rehabilitation protocol involving the occupational therapy team, with exercises and stretching associated with the use of serial extension static braces, dynamics braces and continuous passive movement sessions. The surgical group was submitted to surgical release, followed by the same protocol of rehabilitation of the non surgical group. The clinical scales were applied preoperatively, at 3 and 6 months of follow-up. The range of motion was assessed at the same periods and additionally at 6 weeks. Complications were assessed up to 6 months of treatment. The study primary outcome was the flexion-extension range of motion at 6 months of follow-up. RESULTS: Thirty patients were included in the study, 15 in each group. The elbow flexion-extension range of motion at 6 months of follow-up was 108.4º for the surgical group and 88.1º for the non surgical group (p=0.002). The absolute and relative gain of elbow flexion-extension at 6 months were 17.2º and 26.8% for the non surgical group and 40.8º and 58.8% for the surgical group (p < 0.001). The visual analogue pain scale, the Mayo Elbow Performance Score and the Disability of Arm, Shoulder and Hand questionnaire were respectively 4.4, 70.6 and 35.3 for the non surgical group and 3.9, 77.3 and 27.6 for the surgical group (p=0.486, p=0.342 and p=0.361). The non surgical group presented one complication, while the surgical group had four (p=0.598). CONCLUSIONS: The elbow surgical release associated with the rehabilitation protocol resulted in a greater flexion-extension range of motion and greater absolute and relative gain when compared to the isolated rehabilitation after 6 months. The maximal extension obtained was superior in the surgical group, with no difference for maximal flexion and pronosupination range of motion. The groups did not differ on functional scales and complication rates

A Distrofia Muscular Congênita (DMC) se caracteriza clinicamente por hipotonia e fraqueza muscular, retardo do desenvolvimento motor e retrações fibrotendíneas. Instrumentos de avaliação clínica, como as escalas funcionais, motoras e de qualidade de vida, têm como objetivo quantificar o impacto da doença sobre as atividades diárias da vida do paciente, além de auxiliarem na caracterização de grupos de estudo heterogêneos. Sendo a DMC altamente heterogênea, traçar o perfil funcional dos pacientes com diferentes subtipos seria útil para caracterizar padrões funcionais e auxiliar no tratamento em equipe multidisciplinar. Objetivos: Caracterizar o perfil de funcionalidade e qualidade de vida de pacientes com DMC de diferentes subtipos e correlacioná-lo com a força muscular e grau de amplitude de movimento. Metodologia: Em uma amostra de 18 pacientes com DMC com idade de 12 + 3,2 anos e 13 pacientes com outras miopatias congênitas com idade de 13 + 2,6 anos foram aplicados em três visitas (V1, V2 e V3) os questionários SF-36 e Índice de Barthel (IB), além de realizada avaliação físico-motora (goniometria, força muscular) seguido de correlação com a escala funcional MFM-32 (Medida de Função Motora). Resultados: Houve significativa queda na qualidade de vida em pacientes Merosina (-) e em outras formas de DMC. O índice de Barthel (IB) apontou \"grave dependência\" final em pacientes merosina (-) e \"moderada dependência\" em outras formas de DMC. A goniometria mostrou diminuição da movimentação global em todos os grupos articulares avaliados em pacientes com merosina (-). Em outras formas de DMC, houve exceção de diminuição apenas em articulação distal de membros superiores. A força de todos os grupos musculares é significativamente afetada em ambos os grupos. Pacientes merosina (-) mostram diminuição significativa de funcionalidade nas três dimensões da escala MFM-32 (D1, D2 e D3), e em outras formas de DMC, apenas diminuição em D2 e D3. Houve moderada correlação positiva entre força muscular e D1 da escala MFM-32, forte correlação positiva entre goniometria e D2 e D3 em pacientes com merosina (-), não havendo correlação entre nenhuma variável e MFM-32 em outras formas de DMC. Conclusão: Pacientes com DMC apresentaram perfil funcional \"gravemente dependente\", com diminuição da qualidade de vida, observada em cinco de oito quesitos do questionário SF-36. A força muscular e a amplitude de movimento articular foram afetadas de forma generalizada em ambos os grupos de pacientes. Pacientes com merosina (-) mostraram-se mais afetados funcionalmente em posturas eretas e transferências, sendo correlacionada positivamente com a força muscular dos grupos dessa tarefa / Congenital Muscular Dystrophy (CMD) is characterized by hypotonia and weakness, motor development delay and muscular contractures. Instruments of clinical assessment, such as functional motor and quality of life scales are essential to quantify the impact of the disease on daily activities of the patient\'s life in addition to helping in the characterization of heterogeneous study groups. As the DMC highly heterogeneous, trace the functional profile of patients with different subtypes would be useful to characterize functional patterns and aid in the treatment by a multidisciplinary team. Objectives: To characterize the functionality and quality of life of children with different subtypes of DMC and to correlate them with the degree of muscle strength and range of motion. Methods: In a sample of 18 patients with CMD (aged 12 + 3.2 years) and 13 patients with other congenital myopathies (aged 13 ± 2.6 years) were applied in three visits (V1, V2 and V3) the SF-36 and Barthel Index (BI), and performed physical-motor assessment (goniometry, muscle strength) followed by correlation with functional scale MFM-32 (motor Function Measure. ). Results: There was a significant decrease in the quality of life in patients Merosin (-) and other forms of CMD. IB indicated \"severe dependence\" final in Merosin patients (-) and \"moderate dependence\" in other forms of CMD. Goniometry showed a decrease of the overall joint movement in all groups evaluated in patients with merosin (-).In other forms of DMC was decreased joint movement in all joint groups, except for the distal joint of the upper limbs. The strength of each muscle group was significantly affected in both groups. Patients merosin (-) show a significant decrease in the functionality on the 3 dimensions of MFM-32 scale (D1, D2, D3) in patients with other forms of DMC only reduction in D2 and D3. There was a moderate positive correlation between muscle strength and D1 of the SF-32 scale, strong positive correlation between goniometry and D2 and D3 in patients with Merosin (-), there was no correlation between this variable and MFM-32 in other forms of CMD. Conclusion: Patients with CMD showed functional profile \"severely dependent\" to low quality of life observed in five of eight areas of the SF-36 questionnaire. Muscle strength and range of motion were affected in a generalized manner in both patient groups. Patients with Merosin (-) are even more affected functionally in standing and transfers being positively correlated with muscle strength of the groups of this task postures

Les maladies ostéoarticulaires représentent environ 10% de l’ensemble des pathologiessurvenant en France chaque année. Les difficultés pour identifier les causes de ces maladiesproviennent pour une part d’un manque de compréhension du mécanisme de lubrificationd’une articulation synoviale saine. Dans ce contexte, un premier objectif de ce travail a été d’analyser la structurediscontinue du liquide synovial à partir de prélèvements animaux sains et de la reproduire àpartir de composants biomoléculaires commerciaux afin de comprendre le mécanisme delubrification dans le cas sain. Le deuxième objectif de cette thèse a été d’analyser l’évolution de la structure et despropriétés lubrifiantes du liquide synovial dans le stade précoce de pathologies noninflammatoiresou inflammatoires à partir de prélèvements pathologiques humains. Afind’étudier plus finement l’évolution de la lubrification pathologique cette thèse a visé àdévelopper aussi des modèles de lubrifiants obtenus à partir de cultures cellulaires desynoviocytes humains en combinant l’action de facteurs inflammatoire (cytokines).L’ensemble des résultats montre l’importance de la structure supramoléculaire duliquide synovial dans l’obtention de bonnes propriétés lubrifiantes ; cette relation devraitconstituer d’une part un paramètre clé dans le diagnostic précoce des pathologies articulaireset d’autre part une voie de développement de liquides thérapeutiques à base de lubrifiantsnanostructurés / Osteoarticular diseases account for approximately 10% of all diseases occurring inFrance each year. The difficulties in identifying their causes are also due to a deficiency inunderstanding the lubrication mechanism of healthy synovial joint.In this context, the first objective of the present study was to analyze the discontinuousstructure of synovial fluid samples from healthy animals and to reproduce it using commercialbiomolecular components in order to understand the lubrication mechanism in the healthycase. The second objective of this thesis was to analyze the evolution of the structure andthe lubricating properties of synovial fluid in the early stage of non-inflammatory andinflammatory diseases using pathological human fluid samples. In order to study moreprecisely the evolution of pathological lubrication this work aimed to develop lubricantmodels obtained from cell cultures of human synoviocytes adding the action of pathologicalinflammatory factors (cytokines). All together the results show the importance of the supramolecular structure of thesynovial fluid in obtaining good lubricating properties what may be a key parameter in theearly diagnosis of joint diseases and even more a chance to develop therapeutic fluids basedon nanostructured lubricants