Thesis (M.S.)--University of Missouri--Columbia, 2004. / Typescript. Includes bibliographical references (leaves 63-70). Also issued on the Internet. Also available on the Internet.

Thesis (M.S.)--University of Missouri--Columbia, 2003. / "December 2003." Typescript. Vita. Includes bibliographical references (leaves 84-96). Also issued on the Internet.

O tratamento das lesões condrais e osteocondrais do joelho em pacientes jovens ainda permanece um desafio para os médicos ortopedistas. As técnicas de reparo destas lesões atualmente disponíveis no Brasil, como desbridamento, microfraturas e transplante osteocondral autólogo são insuficientes nos tratamentos das lesões condrais e osteocondrais maiores do que 4 cm2. O transplante osteocondral homólogo a fresco (TOF) na articulação do joelho vem sendo usado em outros países com excelentes resultados. Até o presente momento não existem relatos da utilização desta técnica no Brasil, fato que dificulta o tratamento de pacientes jovens ativos que necessitam de reparo biológico. Foram incluídos neste estudo oito pacientes de 15 a 45 anos portadores de lesões osteocondrais maiores que 4 cm2. Os enxertos a fresco foram obtidos de doadores de órgãos, sendo a articulação do joelho captada sem violação da cápsula articular e transportada ao Banco de Tecidos para processamento. O pareamento doador e receptor foi realizado conforme o tamanho, a localização e a prioridade em lista de espera de acordo com os tecidos captados, sendo os mesmos armazenados no meio de preservação Ham F-12 - GIBCO com glutamax (Invitrogen, Life Technologies, Estados Unidos) e com antibióticos. O procedimento cirúrgico foi realizado pelas técnicas de cilindro osteocondral e de superfície, sendo fixados quando necessário. Os pacientes foram avaliados através dos questionários de IKDC objetivo, IKDC subjetivo, KOOS e índice de Merle D\'Aubigne e Postel modificado. Foram realizados oito TOFs de março a outubro de 2012. A média de idade dos pacientes transplantados foi de 30,1 anos (17- 44 anos) e a média da área transplantada foi de 10,6 cm2 (4,6 - 22,4 cm2). O intervalo médio em dias entre captação e transplante foi de 15,3 (14 - 16 dias) e o número médio de cirurgias prévias ao TOF foi de 2 cirurgias (0-4 cirurgias). A pontuação na escala de IKDC objetiva no pré-operatório foi B em 12%, C em 25% e D em 63% dos pacientes; e 12% A e 88% B aos 18 meses de pós-operatório. A média da pontuação da escala IKDC subjetiva pré-operatória foi de 31,99 ± 13,4 e de 81,84 ± 9,25 em 18 meses de pós-operatório, e da escala KOOS pré-operatória foi de 46,8 ± 20,9 e de 89,58 ± 7,06 em 18 meses de pós-operatório, com melhora significativa ao longo do tempo (p < 0,01) pela análise da variância. A média da pontuação pelo índice de Merle D\'Aubigne e Postel modificado foi de 8,75 ± 2,25 no pré-operatório e de 16,75 ± 2,19 em 18 meses de pós-operatório. O resultado do teste de Friedman para amostras não-paramétricas demonstrou melhora significativa ao longo do tempo (p < 0,01). A padronização da captação, processamento e transplante de enxertos osteocondrais a fresco na articulação do joelho depende de um banco de tecidos altamente especializado e leva a excelentes resultados no tratamento de lesões osteocondrais grandes, sendo atualmente uma boa alternativa de tratamento biológico para pacientes jovens no Brasil / Treatment of chondral and osteochondral lesions of the knee in young patients is still a challenge for Orthopedic Surgeons. The techniques available nowadays in Brazil, as debridement, microfracture and autologous osteochondral transplantation are insufficient for the treatment of chondral and osteochondral lesions larger than 4 cm2. Fresh osteochondral allografts on the knee joint have been used in other countries with great success. Until the present days there are no reports of the utilization of this technique in Brazil, a fact that creates boundaries for the treatment of young active patients that need cartilage repair treatment. Eight patients with age ranging from 15 to 45 years old and osteochondral lesions larger than 4 cm2 were included in this study. Fresh grafts were obtained from organ donors and the knee joint was harvest without violation of synovium capsule and then was transported to the tissue bank for processing. Donor and receptor tissue matching occurred according to size, localization and priority on waiting list and tissue was preserved in Ham F-12 - GIBCO media with glutamax (Invitrogen, Life Technologies, United States) and antibiotics. Surgical procedure was achieved with osteochondral plugs or shell techniques, with additional fixation when needed. Patients were evaluated with IKDC objective, IKDC subjective, KOOS and modified Merle D\'Aubigne-Postel outcome scores. Eight fresh osteochondral allografts were performed from march to october, 2012. The average age was 30.1 years old (17-44) and mean graft surface area was 10.6 cm2 (4.6 - 22.4 cm2). Average time from harvest to transplantation was 15.3 days (14-16 days) and mean number of previous surgical procedures was 2 (0 - 4 procedures). Pre-operative objective IKDC score was B in 12%, C in 25% and D in 63% and was A in 12% and B in 88% in 18 months follow-up. Pre-operative IKDC subjective and KOOS score were 31.99 ± 13.4 and 46.8 ± 20.9; and in 18 months follow-up were 81.84 ± 9.25 and 89.58 ± 7.06, respectively, with a significant increase along time on variance analysis (p < 0.01). Pre-operative mean modified Merle D\'Aubigne-Postel scores were 8.75 ± 2.25 and 16.75 ± 2.19 in 18 months follow-up. Non-parametric Friedman test analysis showed a significant progression in follow-up (p < 0.01). Standards of procurement, processing and utilization of fresh osteochondral allografts in the knee joint relay on a high specialized tissue bank and promote excellent results on the treatment of large osteochondral lesions, being a good alternative of a biologic repair for young patients in Brazil

No description available.

Este estudo objetivou comparar, biomecanicamente, por meio dos ensaios de flexão destrutível e ciclagem, bem como a qualidade da redução óssea, após avaliação do molde da superfície articular de osteotomias centrais do acetábulo de cão fixadas com Clamp and Rod Internal Fixation (CRIF) 2,7 mm ou placa de reconstrução bloqueada 2,7 mm. Os implantes foram divididos em dois grupos, denominados grupo CRIF (GC) e grupo Placa (GP). Foram utilizadas nove pelves de cadáveres de cão com peso corporal entre 15 e 35 kg, posteriormente as pelves foram subdivididas em 18 hemipelves e distribuídas aleatoriamente para testar os dois implantes, um contralateral ao outro em uma mesma pelve. Para realização dos testes, foi simulado uma fratura central no acetábulo, por meio de osteotomia linear, realizada com auxílio de serra oscilatória e em seguida, fixadas segundo os padrões AO/SIF, sendo utilizados três parafusos craniais e dois caudais a osteotomia. Após comparação biomecânica de resistência máxima à flexão o GP (22,38&#177;8,44 N.m) demonstrou superioridade estatística em relação ao GC (15,60&#177;5,76 N.m), (p=0,02408). Na comparação do molde da superfície articular após 30 ciclos o GP (0,27 &#177; 0,24mm) demonstrou valores menores para lacuna da linha articular que o GC (0,49 &#177; 0,29mm), sendo o GP estatisticamente superior, (p=0,04784). Em conclusão, a aplicação da placa de reconstrução bloqueada é simples e deve ser considerada para redução de fraturas do acetábulo que necessitem de reconstrução anatômica. / The aim of this study was to compare the accuracy of reduction and biomechanical characteristics of acetabular osteotomies repaired with 2.7-mm Clamp and Rod Internal Fixation (CRIF) constructs or 2.7-mm locking reconstruction plates in cyclic and load to failure flexion tests. Nine dog cadavers with body weight between 15 and 35 kg were included in this study. All 18 hemipelves were randomly assigned into two groups named after the implants tested, group CRIF (GC) and group Plate (GP). All pelves were used to test both groups with each hemipelvis belonging to a different implant group. Acetabular osteotomies were created with an oscillatory saw and then fixed according to the AO/ASIF standards, using either 5-hole, 2.7-mm locking reconstruction plates with three locked screws cranial and two caudal to the osteotomy line, or CRIF constructs with 5 clamps, three located cranial and two caudal to the osteotomy line. Load to failure at GP (22.38 &#177; 8.44N.m) was significantly higher than GC (15.60 &#177; 5.76N.m), (p = 0.02408). Imprinted cast of acetabular reduction gap after 30 cycles was statistically smaller at GP (0.27 &#177; 0.24mm) than GC (0.49 &#177; 0.29mm) (p = 0.04784). We concluded that the appliance of locking reconstruction plates is simple and should be considered for acetabular fractures, that require perfect anatomical reconstruction.

INTRODUÇÃO: O impacto fêmoro-acetabular (IFA) é considerado importante causa de dor do quadril no jovem, podendo evoluir para osteoartrite do quadril. O objetivo deste estudo foi investigar se há associação entre achados da tomografia computadorizada (TC) em cadáveres e lesões do lábio acetabular avaliadas histologicamente. MÉTODOS: Foram realizadas TCs de bacia de 20 cadáveres não formolizados. Os ângulos habituais relacionados ao IFA foram mensurados por um radiologista (ângulo alfa, versão femoral, versão acetabular, ângulo centro-borda e ângulo de Tönnis). O cadáver foi considerado portador de IFA tipo came quando apresentou um ângulo alfa maior que 50º. O cadáver foi considerado portador de IFA tipo pincer quando apresentou versão acetabular menor que 0º, ângulo centro-borda maior que 40º, ou ângulo de Tönnis menor que 0º. Os cadáveres foram então dissecados, o acetábulo foi ressecado, e três fragmentos foram obtidos da peça correspondendo às porções anterior, superior e posterior do rebordo acetabular. Após preparo histológico habitual, as lesões labiais foram avaliadas por um patologista. Quando presente, a lesão foi classificada segundo Seldes. RESULTADOS: A média de idade dos cadáveres foi de 50,2 anos ± 7,4. Foram estudados 13 homens e 7 mulheres. Dezesseis (80%) dos cadáveres foram considerados portadores de impacto tipo came. Oito (40%) cadáveres foram considerados portadores de impacto tipo pincer. Mulheres apresentaram maior proporção de IFA tipo pincer (21,4% dos homens apresentaram IFA tipo pincer e 83,3% das mulheres, p = 0,01). Histologicamente, 16 (80%) dos espécimes apresentaram lesão microscópica em pelos menos um fragmento. Ao dividirmos as regiões, os fragmentos anteriores apresentaram lesão labial em 65% dos casos, os fragmentos superiores 50% e os fragmentos posteriores em 25%. Segundo a classificação de Seldes, 60,7% das lesões foram do tipo 1, 28,6% foram do tipo 2, e 10,7% foram mistas. Indivíduos com lesão labial apresentaram um ângulo alfa maior (53,3º nos casos com lesão e 49,3º nos casos sem lesão, p = 0,01). Alterações tipo pincer não apresentaram associação com presença de lesões labiais (p > 0,05). Não foi encontrada associação entre pincer ou came e a classificação da lesão labial segundo Seldes (p > 0,05). CONCLUSÕES: Cadáveres com maior ângulo alfa apresentaram maior prevalência de lesão labial. Os demais ângulos analisados não apresentaram associação com a lesão labial. Nenhuma associação foi encontrada entre tipo de IFA e tipo de lesão labial segundo Seldes / INTRODUCTION: Femoroacetabular impingement (FAI) is an important cause of hip pain in the young patient, which may progress to hip arthritis. The purpose of this study was to investigate the relationship between computed tomographic findings in cadavers and histological labral findings. METHODS: Twenty fresh cadavers were submitted to a computed tomography (CT) scan. Standard FAI angles were measured, including alpha angle, femoral version, acetabular version, center-edge, and Tönnis angle. A cam lesion was defined as an alpha angle greater than 50º. A pincer lesion was defined as acetabular version less than 0º, or center-edge angle greater than 40º, or Tönnis angle less than 0º. Cadavers were dissected, the acetabulum was resected, and three fragments of each acetabuli were obtained corresponding to the anterior, superior and posterior acetabular rim. Following routine histological preparation, the histological slides were evaluated for possible labral tears. Tears were classified by Seldes type. RESULTS: The cadavers\' mean age was 50.2 years (SD: 7.4), 13 were males, 7 females. Sixteen (80%) specimens had a cam lesion. Eight (40%) specimens had a pincer lesion. Females were more likely to present a pincer lesion (21.4% males versus 83.3% females, p = 0.01). Histologically, 16 (80%) specimens had a labral tear in at least one region. When divided by region; anterior labra had lesions in 65% of cases; superior labra in 50% and posterior labra in 25%. According to Seldes classification, 60.7% of labral tears were type 1, 28.6% were type 2, and 10.7% were mixed. Patients who had a labral tear had significantly higher alpha angles (53.3º versus 49.3º, p = 0.01). Pincer lesions were not associated with labral tears (p > 0.05). We found no association between pincer or cam lesions and Seldes classification (p > 0.05). CONCLUSIONS: Cadavers presenting with higher alpha angles had higher prevalence of labral tears. Other FAI angles had no association with labral tears. No association was found between FAI type and Seldes classification

Background: The impairment of articular cartilage caused by trauma or degenerative pathology is one of the most challenging issues in clinical Orthopedics because of the limited intrinsic regenerative capability of this tissue. Hypoxia is a major stimulus to initiate gene programs in regulating chondrogenic lineage cell functions during cartilage development and regeneration. Hypoxia-inducible factor-1α (HIF-1α), the key transcription factor to sense oxygen fluctuations of cells, is abundantly expressed in the cartilage and considered as a potential therapeutic target for cartilage tissue homeostasis or repair. However, the molecular mechanisms and therapeutic efficacy of targeting the HIF-1α pathway remain to be well defined. / Methods: Osteochondral defect mouse model was generated to examine the hypoxia states during articular cartilage repair with the Hypoxyprobe. Specific HIF-1α deletion in the repairing tissue was established to determine its regulatory role during cartilage restoration. Deferoxamine (DFO), stabilizing HIF-1α from proteolysis by inhibiting the prolyl hydroxylases (PHDs), was investigated systemically on the function of chondroprogenitors and mesenchymal stem cells (MSCs) in vitro. Alcian blue staining determined the proteoglycan synthesis. HIF components, chondrogenic related genes and proteins were examined by quantitative PCR, western blotting and immunohistochemistry, respectively. The proliferation, differentiation and migration assays were performed to determine the influence of DFO onchondroprogenitors and MSCs. The recruitment or engraftment of MSCs in the injured site was traced by transplantation of GFP-labeled MSCs adjacent to the defect region, and examined by immunofluorescence staining. DFO incorporated in a 3D alginate-gelfoam scaffold was analyzed for its therapeutic effects on the articular cartilage regeneration. At 6 and 12 weeks following surgery, the cartilage tissue repair was scored and the expression of proliferating cell nuclear antigen (PCNA), Sox9 and collagen typeⅡ(Col2) was examined by immunohistochemistry. / Results: Hypoxia states and the expression of HIF-1α in the repair tissue were ubiquitously existed in the osteochondral defect model. DFO significantly upregulated HIF-1α expression and nuclear localization, and increased the levels of PHDs. DFO increased chondroprogenitor cell proliferation as visualized by colony forming unit assay, which was in accord with the upregulation of cyclin D1. DFO significantly induced chondrogenic differentiation indexed by increased Col2 and Sox9 protein expression and elevated proteoglycan synthesis. With sustained upregulation of HIF-1α DFO was supposed to effectively promote chondrogenesis in mimic of hypoxic microenvironment. DFO also increased the migration of MSCs, and elevated the expression of tissue inhibitor metalloproteinase-3 (TIMP3) through transcriptional control by HIF-1α. Furthermore, DFO initiated MSCs membrane protrusion through regulating the expression and interaction of the key focal adhesion proteins vinculin and paxillin. In vivo study showed that DFO dramatically facilitated the recruitment and functional engraftment of MSCs to the lesion site compared with the controls. Alginate-gelfoam scaffold incorporated with DFO enhanced articular cartilage repair through increasing chondrogenic cell proliferation, differentiation and proteoglycan synthesis. The enhanced therapeutic effect of DFO on articular cartilage repair was eliminated following HIF-1α deletion in the repairing cells of the cartilage lesion. The results indicate that the positive effect of DFO on articular cartilage repair is at least partially mediated by HIF-1α. / Conclusion: HIF-1α is an essential mediator during articular cartilage repair. Activation of HIF-1α by PHD inhibitor DFO increases chondroprogenitor cell proliferation, differentiation and migration in vitro. DFO enhances articular cartilage repair through coordinating MSCs migration, chondrogenic differentiation and functional engraftment. The results provide proof of principle that targeting the HIF-1α pathway may serve as a novel approach for promoting articular cartilage regeneration. / 背景：关节软骨自愈能力非常有限，由创伤或退行性病变引起关节软骨损伤的治疗是骨科领域的一大难题。在软骨发育和再生过程中，低氧条件对启动基因表达及调控软骨系细胞功能至关重要。低氧诱导因子-1α（HIF-1α）作为关键的转录因子可感应细胞外氧含量变化，广泛存在于软骨组织中，并被认为对维持软骨组织内稳态及促进软骨修复有重要作用。然而，以HIF-1α 通路为靶点的小分子靶向药物的分子机制与治疗效果尚不明确。 / 方法：本课题系统性地研究了HIF 信号通路激活剂去铁胺（DFO）对软骨损伤的作用。我们构建了骨软骨缺损模型，应用缺氧探针检测了软骨缺损过程中修复组织的低氧状态，并特异性敲除软骨修复组织中HIF-1α 表达，研究其在软骨再生过程中的调节作用。我们用阿利新蓝染色检测软骨细胞蛋白多糖的合成及分泌。通过实时荧光定量聚合酶链式反应，免疫印迹以及免疫组化等方法检测了HIF 家族成员和软骨分化标志物的基因和蛋白含量变化。通过增殖及迁移实验检测了DFO 对软骨细胞或者骨髓间充质干细胞（MSC）功能的影响。另外，我们还将GFP 标记的MSC 注射到与小鼠软骨缺损区域相邻的软骨下骨中，观察其在软骨缺损模型中的募集及功能性植入。我们以藻酸盐和明胶海绵复合物为给药系统，包载DFO 并作用于关节软骨缺损部位。术后6 周及12 周取材，以番红O 染色检测DFO 对小鼠关节软骨缺损的修复效果，并通过免疫组化检测增殖细胞核抗原（PCNA），Sox9 以及Col2 等蛋白的表达。 / 结果：低氧状态和HIF-1α 在骨软骨缺损模型中的软骨缺损区域广泛存在和表达。DFO 显著提高了HIF-1α 蛋白表达及转运入核，增加了脯氨酸羟化酶（PHD）表达。在软骨祖细胞中，DFO 可提高其增殖、克隆能力，并增加周期蛋白D1的表达。同时，DFO 能明显促进软骨祖细胞分化，增加软骨分化标志物基因以及Sox9 和Col2 蛋白表达，提高蛋白多糖分泌。通过持续性激活HIF-1α，DFO可模仿低氧微环境来提高软骨细胞增殖、分化能力。分子机制研究发现，DFO激活HIF-1α 后，HIF-1α 作用在靶基因金属蛋白酶组织抑制剂-3 启动子上，增加其转录和蛋白表达，进而提高MSC 的迁移能力。另外，激活HIF-1α 蛋白可增加黏着斑蛋白，桩蛋白表达以及它们的相互作用，促进MSC 伪足延伸。体内实验中，通过追踪小鼠体内GFP 标记的MSC 发现， DFO 可在软骨损伤早期（7 天及14 天）提高受损部位MSC 募集数量，并促进其向软骨细胞谱系分化。通过增加软骨系细胞增殖、分化、蛋白多糖合成，包载DFO 的藻酸盐明胶海绵给药系统显著提高了软骨缺损组织的修复效果。而在软骨修复组织中特异性敲除HIF-1α 蛋白后，明显降低了DFO 对软骨缺损的治疗效果，提示DFO对软骨修复的作用至少部分由HIF-1α 介导。 / 结论：HIF-1α 是关节软骨修复过程中的重要调控因子。PHD 抑制剂DFO 可以激活HIF-1α 表达，增加软骨祖细胞增殖、分化和迁移。DFO 通过调控MSC 募集、软骨细胞谱系分化以及功能性植入，明显改善关节软骨再生修复的效果。本研究为HIF-1α 信号通路作为一种新的治疗靶点促进关节软骨再生提供了重要证据。 / Shu, Yinglan. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 155-181). / Abstracts also in Chinese. / Title from PDF title page (viewed on 09, September, 2016). / Shu, Yinglan. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Experimental Surgery, Department of Surgery. Title from pdf file main screen (viewed on April 24, 2010). Includes bibliographical references.

INTRODUÇÃO: O impacto fêmoro-acetabular (IFA) é considerado importante causa de dor do quadril no jovem, podendo evoluir para osteoartrite do quadril. O objetivo deste estudo foi investigar se há associação entre achados da tomografia computadorizada (TC) em cadáveres e lesões do lábio acetabular avaliadas histologicamente. MÉTODOS: Foram realizadas TCs de bacia de 20 cadáveres não formolizados. Os ângulos habituais relacionados ao IFA foram mensurados por um radiologista (ângulo alfa, versão femoral, versão acetabular, ângulo centro-borda e ângulo de Tönnis). O cadáver foi considerado portador de IFA tipo came quando apresentou um ângulo alfa maior que 50º. O cadáver foi considerado portador de IFA tipo pincer quando apresentou versão acetabular menor que 0º, ângulo centro-borda maior que 40º, ou ângulo de Tönnis menor que 0º. Os cadáveres foram então dissecados, o acetábulo foi ressecado, e três fragmentos foram obtidos da peça correspondendo às porções anterior, superior e posterior do rebordo acetabular. Após preparo histológico habitual, as lesões labiais foram avaliadas por um patologista. Quando presente, a lesão foi classificada segundo Seldes. RESULTADOS: A média de idade dos cadáveres foi de 50,2 anos ± 7,4. Foram estudados 13 homens e 7 mulheres. Dezesseis (80%) dos cadáveres foram considerados portadores de impacto tipo came. Oito (40%) cadáveres foram considerados portadores de impacto tipo pincer. Mulheres apresentaram maior proporção de IFA tipo pincer (21,4% dos homens apresentaram IFA tipo pincer e 83,3% das mulheres, p = 0,01). Histologicamente, 16 (80%) dos espécimes apresentaram lesão microscópica em pelos menos um fragmento. Ao dividirmos as regiões, os fragmentos anteriores apresentaram lesão labial em 65% dos casos, os fragmentos superiores 50% e os fragmentos posteriores em 25%. Segundo a classificação de Seldes, 60,7% das lesões foram do tipo 1, 28,6% foram do tipo 2, e 10,7% foram mistas. Indivíduos com lesão labial apresentaram um ângulo alfa maior (53,3º nos casos com lesão e 49,3º nos casos sem lesão, p = 0,01). Alterações tipo pincer não apresentaram associação com presença de lesões labiais (p > 0,05). Não foi encontrada associação entre pincer ou came e a classificação da lesão labial segundo Seldes (p > 0,05). CONCLUSÕES: Cadáveres com maior ângulo alfa apresentaram maior prevalência de lesão labial. Os demais ângulos analisados não apresentaram associação com a lesão labial. Nenhuma associação foi encontrada entre tipo de IFA e tipo de lesão labial segundo Seldes / INTRODUCTION: Femoroacetabular impingement (FAI) is an important cause of hip pain in the young patient, which may progress to hip arthritis. The purpose of this study was to investigate the relationship between computed tomographic findings in cadavers and histological labral findings. METHODS: Twenty fresh cadavers were submitted to a computed tomography (CT) scan. Standard FAI angles were measured, including alpha angle, femoral version, acetabular version, center-edge, and Tönnis angle. A cam lesion was defined as an alpha angle greater than 50º. A pincer lesion was defined as acetabular version less than 0º, or center-edge angle greater than 40º, or Tönnis angle less than 0º. Cadavers were dissected, the acetabulum was resected, and three fragments of each acetabuli were obtained corresponding to the anterior, superior and posterior acetabular rim. Following routine histological preparation, the histological slides were evaluated for possible labral tears. Tears were classified by Seldes type. RESULTS: The cadavers\' mean age was 50.2 years (SD: 7.4), 13 were males, 7 females. Sixteen (80%) specimens had a cam lesion. Eight (40%) specimens had a pincer lesion. Females were more likely to present a pincer lesion (21.4% males versus 83.3% females, p = 0.01). Histologically, 16 (80%) specimens had a labral tear in at least one region. When divided by region; anterior labra had lesions in 65% of cases; superior labra in 50% and posterior labra in 25%. According to Seldes classification, 60.7% of labral tears were type 1, 28.6% were type 2, and 10.7% were mixed. Patients who had a labral tear had significantly higher alpha angles (53.3º versus 49.3º, p = 0.01). Pincer lesions were not associated with labral tears (p > 0.05). We found no association between pincer or cam lesions and Seldes classification (p > 0.05). CONCLUSIONS: Cadavers presenting with higher alpha angles had higher prevalence of labral tears. Other FAI angles had no association with labral tears. No association was found between FAI type and Seldes classification

The Runx family of transcription factors supports cell fate determination, cell cycle regulation, global protein synthesis control, and genetic as well as epigenetic regulation of target genes. Runx1, which is essential for hematopoiesis; Runx2, which is required for osteoblast differentiation; and Runx3, which is involved in neurologic and gut development; are expressed in the growth plate during chondrocyte maturation, and in the chondrocytes of permanent cartilage structures. While Runx2 is known to control genes that contribute to chondrocyte hypertrophy, the functions of Runx1 and Runx3 during chondrogenesis and in cartilage tissue have been less well studied. The goals of this project were to characterize expression of Runx proteins in articular cartilage and differentiating chondrocytes and to determine the contribution of Runx1 to osteoarthritis (OA). Here, the expression pattern of Runx1 and Runx2 was characterized in normal bovine articular cartilage. Runx2 is expressed at higher levels in deep zone chondrocytes, while Runx1 is primarily expressed in superficial zone chondrocytes, which is the single cell layer that lines the surface of articular cartilage. Based on this finding, the hypothesis was tested that Runx1 is involved in osteoarthritis, which is a disease characterized by degradation of articular cartilage and changes in chondrocytes. These studies showed that Runx1 is upregulated in articular cartilage explants in response to mechanical compression. Runx1 was also expressed in chondrocytes found at the periphery of OA lesions in the articular cartilage of mice that underwent an OA-inducing surgery. Runx1 was also upregulated in cartilage explants of human osteoarthritic knees, and IHC data showed that Runx1 is mainly expressed in chondrocyte “clones” characteristic of OA. To ascertain the potential function of the upregulation of Runx1 in these cartilage stress conditions and disease states, the hypothesis was tested that Runx1 is upregulated in very specific chondrocyte populations in response to the cartilage damage in osteoarthritis. These studies addressed the properties of these cells that related to functions in cell growth and differentiation. In both the surface layer of normal articular cartilage, and in OA cartilage, Runx1 expression by IF co-localized with markers of mesenchymal progenitor cells, as well as markers of proliferation Ki-67 and PCNA. This finding indicated that Runx1 is found in a population of cells that represent a proliferative population of mesenchymal progenitor cells in osteoarthritis. To further address Runx1 function and identify downstream targets of Runx proteins, a promoter analysis of genes that are known to be either downregulated or upregulated during chondrocyte maturation was done. These studies found that many of these genes have 1 or more Runx binding sites within 2kb of their transcription start site, indicating that they are potential downstream Runx target genes. Lastly, some preliminary experiments were done to characterize novel roles of Runx proteins in the chondrocyte. Runx proteins have been shown to epigenetically regulate their target genes by remaining bound to them throughout mitosis, “poising” them for transcription upon exit from mitosis. The hypothesis that Runx proteins also function by remaining bound to their target genes throughout mitosis in chondrocytes was tested. It was demonstrated by immunofluorescense imaging of Runx proteins on metaphase chromosomes of ATDC5 cells, that Runx2 remains bound to chromosomes during mitosis. Cell proliferation and hypertrophy are both linked to increases in protein synthesis. Runx factors, which regulate rates of global protein synthesis, are expressed in both proliferating and hypertrophic chondrocytes. Thus, it was hypothesized that Runx proteins regulate rates of global protein synthesis during chondrocyte maturation. These studies showed that the overexpression of Runx proteins in a chondrocyte cell line (ATDC5) did not affect protein synthesis rates or levels of protein synthesis machinery. Additionally, Runx proteins did not affect proliferation rates in this chondrocyte cell line.