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2.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360771

RESUMO

Inflammation plays a central role in the pathogenesis of knee PTOA after knee trauma. While a comprehensive therapy capable of preventing or delaying post-traumatic osteoarthritis (PTOA) progression after knee joint injury does not yet clinically exist, current literature suggests that certain aspects of early post-traumatic pathology of the knee joint may be prevented or delayed by anti-inflammatory therapeutic interventions. We discuss multifaceted therapeutic approaches that may be capable of effectively reducing the continuous cycle of inflammation and concomitant processes that lead to cartilage degradation as well as those that can simultaneously promote intrinsic repair processes. Within this context, we focus on early disease prevention, the optimal timeframe of treatment and possible long-lasting sustained delivery local modes of treatments that could prevent knee joint-associated PTOA symptoms. Specifically, we identify anti-inflammatory candidates that are not only anti-inflammatory but also anti-degenerative, anti-apoptotic and pro-regenerative.


Assuntos
Anti-Inflamatórios/uso terapêutico , Traumatismos do Joelho , Osteoartrite do Joelho , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Humanos , Traumatismos do Joelho/complicações , Traumatismos do Joelho/tratamento farmacológico , Traumatismos do Joelho/metabolismo , Traumatismos do Joelho/patologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia
3.
Medicine (Baltimore) ; 100(28): e26659, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260572

RESUMO

RATIONALE: Tenosynovial giant cell tumor (TGCT) is a neoplastic, inflammatory disease with a benign but aggressive course that often presents as localized (TGCT-L) and diffuse (TGCT-D) forms based on the growth pattern and clinical behavior. For TGCT-L, simple excision of the diseased synovial tissue is the preferred treatment option, while for TGCT-D, adequate synovectomy is usually tricky but is essential. However, approximately 44% of TGCT-D cases will relapse after surgery alone. Thus, the optimal treatment strategy in patients with TGCT-D is evolving, and standalone surgical resection can no longer be regarded as the only treatment. The previous studies have shown that postoperative adjuvant radiotherapy can reduce recurrence in TGCT, especially in patients with incomplete synovectomy. PATIENT CONCERNS: In the first case, a 54-year-old male presented with recurrent pain and swelling of the right knee with a protracted disease course (≥10 years). The other patient is a 64-year-old male who developed swelling, pain, abnormal bending, and limited movement of the left knee without obvious inducement. DIAGNOSES: Clinical and imaging examinations can provide a definitive diagnosis, and pathology is the gold standard. TGCT-D was confirmed by postoperative pathology. After the operation, the patients underwent an MRI re-examination and showed that the lesions of the knee were not completely resected. INTERVENTIONS: Arthroscopic synovectomy was performed on the patients, and postoperative pathology was confirmed as TGCT-D. Because of incomplete synovectomy, the 2 cases received image-guided, intensity-modulated radiotherapy (IG-IMRT) after the operation. OUTCOMES: The follow-up time was 1 year, no evidence of disease progression was found in MRI. No obvious adverse effects associated with radiotherapy were detected during the follow-up period. LESSONS: These cases and reviews illustrate the necessity of radiotherapy for TGCT-D and that IG-IMRT is a safe and effective method for treating TGCT-D of the knee.


Assuntos
Tumor de Células Gigantes de Bainha Tendinosa/radioterapia , Articulação do Joelho/patologia , Radioterapia Guiada por Imagem/métodos , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico por imagem , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sinovectomia
4.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281202

RESUMO

Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients.


Assuntos
Condrócitos/transplante , Animais , Doenças das Cartilagens/cirurgia , Doenças das Cartilagens/terapia , Cartilagem Articular/cirurgia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Condrócitos/citologia , Condrócitos/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Humanos , Traumatismos do Joelho/cirurgia , Traumatismos do Joelho/terapia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Procedimentos Ortopédicos/métodos , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/terapia , Esferoides Celulares , Transplante Autólogo
5.
Acta Orthop Traumatol Turc ; 55(3): 239-245, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100365

RESUMO

OBJECTIVE: The aim of this study was to compare the effect of Gap Balancing (GB) versus Measured Resection (MR) techniques on the early clinical and radiological results of Total Knee Arthroplasty (TKA). METHODS: In this prospective study, 99 patients (99 knees) who underwent unilateral TKA between March 2018 and January 2019 were randomly allocated to one of two groups: The GP group, TKA with GB technique (19 male, 31 female; mean age = 55.9 ±16.5) and the MR group, TKA with MR technique (19 male, 30 female; mean age = 54.2 ± 18.7). Patients in both groups were comparable in terms of the demographic and clinical data. The angle of cutting block to PCA and Cutting Thickness of the Medial and Lateral Condyle (CTMC, CTLC) were intraoperatively measured. In radiographic analysis, Preoperative Mechanical Femorotibial Angle (Pre-mFTA), Postoperative Mechanical Femorotibial Angle (Post-mFTA), and joint line changes were examined. Femoral component Rotation Angle (FCRA) was also measured by computed tomography. In gait analysis, the spatiotemporal parameters (walking speed, step length, and single support time) and kinematics parameters (flexion angle, extension angle, and transversal rotation) were collected at 12 months postoperatively. Furthermore, Western Ontario and McMaster Universities Arthritis Index (WOMAC) were performed at 12 months after surgery. RESULTS: CTMC and CTLC were both significantly higher in GB group than in the MR group (9.8±2.0 mm vs 8.5 ± 1.2 mm; 7.9 ± 1.8mm vs 6.8 ± 1.4mm; P = 0.001, P = 0.002, respectively). Angle of cutting block to PCA was statistically lower in GB group than in the MR group (1.7 ± 1.5° vs 3.1 ± 0.5 °; P < 0.001). FCRA is greater in the GB group compared to the MR group, but the difference did not reach statistical significance (1.2 ± 2.8 ° vs 0.7 ± 2.0 °; P > 0.05). Although post-mFTA significantly improved compared with pre-mFTA in both groups, no significant difference was observed in the changes of post-mFTA between the two groups (0.9 ± 1.7° vs 0.3 ± 1.8°, P > 0.05). No significant differences were determined between the two groups in spatiotemporal gait parameters including walking speed, step length, and single support time. The sagittal max knee flexion range was significantly larger in the GB group than in the MR group (49.27 ± 5.24 ° vs 45.99 ± 8.21 °, P < 0.05). The flexion range did not reach the level of the control group. There was no significant difference between the two groups in WOMAC at 12 months follow-up (P > 0.05). CONCLUSION: Evidence from this study has revealed GB and MR techniques have both little effect on early clinical results of TKA. Nonetheless, GB technique can provide better knee flexion in the early postoperative gait status compared with MR technique. LEVEL OF EVIDENCE: Level I, Therapeutic Study.


Assuntos
Artroplastia do Joelho , Osso e Ossos , Articulação do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Pesos e Medidas Corporais/métodos , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Feminino , Análise da Marcha/métodos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/cirurgia , Avaliação de Resultados em Cuidados de Saúde/métodos , Amplitude de Movimento Articular , Análise Espaço-Temporal , Tomografia Computadorizada por Raios X/métodos
6.
Clin Nutr ; 40(5): 2483-2490, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932790

RESUMO

BACKGROUND & AIMS: The evidence of benefiting from a high-quality diet for knee osteoarthritis (OA) joint structures, symptoms, and systemic abnormalities is limited. Clarifying the relationship between diet quality and knee OA could provide useful information for knee OA management. To investigate the associations between diet quality and knee joint structures, symptoms, lower limb muscle strength, depressive symptoms, and quality of life in people with knee OA. METHODS: This study was a post-hoc, exploratory analysis using data from a randomized controlled trial in symptomatic knee OA participants with a follow-up time of 24 months. In brief, eligible participants of the original study were aged 50-79 years, had symptomatic knee OA, and had a pain of 20-80 mm on a 100-mm visual analog scale. After excluding the patients without information on diet quality, 392 participants were included in this post-hoc analysis. Diet quality was assessed at baseline using the Australian Recommended Food Score (ARFS) which includes subscores of vegetable, fruit, grain, dairy products, fat, and alcohol. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume assessed by magnetic resonance imaging), OA symptoms, lower limb muscle strength, depressive symptoms, and quality of life were assessed at baseline and follow up. Mixed-effects models were used to assess the associations of diet quality with those outcomes. RESULTS: Diet quality mainly reflect diet variety within the core food was not associated with knee structures and OA symptoms, but was associated with greater lower limb muscle strength (ß = 0.66, P = 0.001), lower depressive symptom (ß = -0.08, P = 0.001), and better quality of life (ß = -0.06, P = 0.002). In further analyses of food group-based sub-scores, only the vegetable sub-score had the similar associations with lower limb muscle strength (ß = 1.03, P = 0.004), depressive symptom (ß = -0.17, P < 0.001), and quality of life (ß = -0.14, P < 0.001). CONCLUSIONS: Higher diet quality, mainly vegetable diet quality, is associated with greater lower limb muscle strength, less depressive symptoms, and higher quality of life in knee OA patients, suggesting higher diet quality may have protective effects on knee OA.


Assuntos
Dieta/normas , Articulação do Joelho/patologia , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida
7.
Biomed Res Int ; 2021: 6614122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997024

RESUMO

Background: Spontaneous osteonecrosis of the knee (SONK) can lead to severe knee osteoarthritis predominantly localized to the medial compartment. We aimed to determine whether unicompartmental knee arthroplasty was an effective treatment for primary SONK. Methods: We analyzed the functional outcomes in 23 patients with SONK (with a magnetic resonance imaging- (MRI-) confirmed diagnosis) who underwent UKA at a single center. The mean follow-up time was 67 months post-UKA. Results: Significant improvements in function were indicated by reduced Oxford Knee and Visual Analogue Scale scores after UKA, and there were no specific complications after the procedures. The incidence of MRI-identified medial meniscus posterior root tear (MMPRT) was 69.6% (16/23). Conclusion: Unicompartmental arthroplasty for SONK is less destructive to the native knee structure than total knee arthroplasty but can achieve comparable prognosis with strict patient selection. While the precise etiology of SONK is unknown, one theory posits that a MMPRT may change the biomechanical circumstances of the knee joint, leading to osteonecrosis. Although not confirmatory, the high prevalence rate suggests that MMPRT may have a key role in the development of SONK. UKA is an effective treatment option for SONK, resulting in significant functional improvement. Long-term (>10 years) outcomes should be investigated.


Assuntos
Artroplastia do Joelho , Articulação do Joelho/patologia , Meniscos Tibiais/patologia , Osteonecrose/complicações , Lesões do Menisco Tibial/epidemiologia , Lesões do Menisco Tibial/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Articulação do Joelho/diagnóstico por imagem , Masculino , Meniscos Tibiais/diagnóstico por imagem , Pessoa de Meia-Idade , Osteonecrose/diagnóstico por imagem , Estudos Retrospectivos , Lesões do Menisco Tibial/complicações , Lesões do Menisco Tibial/diagnóstico por imagem , Resultado do Tratamento
8.
Eur J Med Chem ; 221: 113514, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992926

RESUMO

While anti-inflammatory properties of isocoumarins are known their PDE4 inhibitory potential was not explored previously. In our effort the non-PDE4 inhibitor isocoumarins were transformed into the promising inhibitors via introducing an aminosulfonyl/aminocarboxamide moiety to the C-3 benzene ring attached to the isocoumarin framework. This new class of isocoumarins were synthesized via a PdCl2-catalyzed construction of the 4-allyl substituted 3-aryl isocoumarin ring starting from the appropriate 2-alkynyl benzamide derivative. Several compounds showed good inhibition of PDE4B in vitro and the SAR indicated superiority of aminosulfonamide moiety over aminocarboxamide in terms of PDE4B inhibition. Two compounds 3q and 3u with PDE4B IC50 = 0.43 ± 0.11 and 0.54 ± 0.19 µM and ≥ 2-fold selectivity over PDE4D emerged as initial hits. The participation of aminosulfonamide moiety in PDE4B inhibition and the reason for selectivity though moderate shown by 3q and 3u was revealed by the in silico docking studies. In view of potential usefulness of moderately selective PDE4B inhibitors the compound 3u (that showed PDE4 selectivity over other PDEs) was further evaluated in adjuvant induced arthritic rats. At an intraperitoneal dose of 30 mg/kg the compound showed a significant reduction in paw swelling (in a dose dependent manner), inflammation and pannus formation (in the knee joints) as well as pro-inflammatory gene expression/mRNA levels and increase in body weight. Moreover, besides its TNF-α inhibition and no significant toxicity in an MTT assay the compound did not show any adverse effects in a thorough toxicity studies e.g. teratogenicity, hepatotoxicity, cardiotoxicity and apoptosis in zebrafish. Thus, the isocoumarin 3u emerged as a new, safe and moderately selective PDE4B inhibitor could be useful for inflammatory diseases possibly including COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Isocumarinas/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/toxicidade , Artrite Experimental/patologia , Catálise , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Feminino , Isocumarinas/síntese química , Isocumarinas/metabolismo , Isocumarinas/toxicidade , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Paládio/química , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/metabolismo , Inibidores da Fosfodiesterase 4/toxicidade , Ligação Proteica , Células RAW 264.7 , Ratos Wistar , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/metabolismo , Sulfonamidas/toxicidade , Peixe-Zebra
9.
Knee ; 30: 100-105, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33887620

RESUMO

BACKGROUND: Although computer navigation has improved component alignment in total knee arthroplasty (TKA), radiographic outliers are reported with a wide range in literature even using this technique. We hypothesized that the postoperative malalignment after computer-navigated TKA was partially derived from the inherent problems with two-dimensional (2D) measurement such as inaccuracies in measurement due to the knee position during the radiographic examination and the direction of the X-ray beam. We therefore conducted this study to determine how often knees with malalignment on 2D imaging were truly mal-aligned on three-dimensional (3D) reconstructed imaging. METHODS: Sixty-two computer-navigated primary TKAs performed in 47 patients were included in this study. In all cases, a weight-bearing long-leg radiograph was obtained after TKA. 3D measurements were performed for outliers 2° or more in coronal alignment of the femoral or tibial component. RESULTS: For the 18 femoral mal-aligned components on 2D imaging, eight (44.4%) were not truly mal-aligned on 3D imaging (P = 0.0014). For the eight tibial mal-aligned components on 2D imaging, all knees (100%) were not truly mal-aligned on 3D imaging (P < 0.0001). CONCLUSIONS: A considerable number of the false malalignments were included on 2D measurement. Postoperative component alignment in the computer-navigated TKA might be much better than previously reported.


Assuntos
Artroplastia do Joelho/efeitos adversos , Mau Alinhamento Ósseo/diagnóstico por imagem , Articulação do Joelho/patologia , Cirurgia Assistida por Computador/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/métodos , Mau Alinhamento Ósseo/etiologia , Computadores , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Imageamento Tridimensional , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Período Pós-Operatório , Radiografia , Radiografia Intervencionista , Cirurgia Assistida por Computador/métodos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia
10.
Theranostics ; 11(11): 5160-5173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859740

RESUMO

Objectives: Disruption of anisotropic phenotypes of the meniscus would contribute to OA progression. Exploring phenotype changes of the anisotropic meniscus in joint degeneration would help understand the biologic interaction between the meniscus and OA, and further facilitate the therapeutic strategies of meniscus injury-related joint degeneration. Meanwhile, engineering biomimetic meniscal tissue mimicking the anisotropy of the healthy meniscus remains a challenge. Methods & Results: Meniscal disruption of phenotype anisotropy (PBV growth, cellular phenotype and ECM depositions) was confirmed in OA patient samples. To recapitulate healthy meniscus phenotypes, 3D-bioprinted anisotropic TCM meniscus constructs with PBV growth and regional differential cell and ECM depositions were generated. Transplanted 3D-bioprinted meniscus into rabbit knees recapitulated phenotypes of native healthy meniscus and conferred long-term protection against secondary joint degeneration. Conclusion: 3D-bioprinted TCM meniscus not only restored the anisotropy of native healthy meniscus with PBV infiltration and better shape retention, but better maintained joint function and prevented secondary joint degeneration, which provided a new strategy for the clinical treatment of meniscus injury-related joint degenerative diseases.


Assuntos
Articulação do Joelho/patologia , Menisco/patologia , Engenharia Tecidual/métodos , Animais , Anisotropia , Bioimpressão/métodos , Fenótipo , Coelhos
11.
Int J Mol Sci ; 22(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800401

RESUMO

Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.


Assuntos
Anti-Inflamatórios/uso terapêutico , Osteoartrite do Joelho/terapia , Plasma Rico em Plaquetas , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Injeções Intra-Articulares , Articulação do Joelho/imunologia , Articulação do Joelho/patologia , Osteoartrite do Joelho/imunologia , Osteoartrite do Joelho/patologia
12.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802838

RESUMO

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.


Assuntos
Cartilagem Articular/metabolismo , Articulação do Joelho/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Osteoartrite do Joelho/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Trombospondinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Condrócitos/metabolismo , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Transporte Proteico
13.
PLoS Genet ; 17(4): e1009275, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33819267

RESUMO

Mammalian Hedgehog (HH) signalling pathway plays an essential role in tissue homeostasis and its deregulation is linked to rheumatological disorders. UBR5 is the mammalian homologue of the E3 ubiquitin-protein ligase Hyd, a negative regulator of the Hh-pathway in Drosophila. To investigate a possible role of UBR5 in regulation of the musculoskeletal system through modulation of mammalian HH signaling, we created a mouse model for specific loss of Ubr5 function in limb bud mesenchyme. Our findings revealed a role for UBR5 in maintaining cartilage homeostasis and suppressing metaplasia. Ubr5 loss of function resulted in progressive and dramatic articular cartilage degradation, enlarged, abnormally shaped sesamoid bones and extensive heterotopic tissue metaplasia linked to calcification of tendons and ossification of synovium. Genetic suppression of smoothened (Smo), a key mediator of HH signalling, dramatically enhanced the Ubr5 mutant phenotype. Analysis of HH signalling in both mouse and cell model systems revealed that loss of Ubr5 stimulated canonical HH-signalling while also increasing PKA activity. In addition, human osteoarthritic samples revealed similar correlations between UBR5 expression, canonical HH signalling and PKA activity markers. Our studies identified a crucial function for the Ubr5 gene in the maintenance of skeletal tissue homeostasis and an unexpected mode of regulation of the HH signalling pathway.


Assuntos
Artrite Reumatoide/genética , Proteínas de Drosophila/genética , Músculo Esquelético/metabolismo , Receptor Smoothened/genética , Ubiquitina-Proteína Ligases/genética , Animais , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Cartilagem/crescimento & desenvolvimento , Cartilagem/metabolismo , Cartilagem/patologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Drosophila melanogaster/genética , Proteínas Hedgehog/genética , Homeostase/genética , Humanos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Camundongos , Músculo Esquelético/patologia , Osteogênese/genética , Transdução de Sinais/genética , Tendões/metabolismo , Tendões/patologia
15.
Am J Med Genet A ; 185(6): 1691-1699, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33713555

RESUMO

Bartsocas-Papas syndrome (BPS) is a rare autosomal recessive disorder characterized by popliteal pterygia, syndactyly, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and genital malformations. Most of the BPS cases reported to date are fatal either in the prenatal or neonatal period. Causative genetic defects of BPS were mapped on the RIPK4 gene encoding receptor-interacting serine/threonine kinase 4, which is critical for epidermal differentiation and development. RIPK4 variants are associated with a wide range of clinical features ranging from milder ectodermal dysplasia to severe BPS. Here, we evaluated a consanguineous Turkish family, who had two pregnancies with severe multiple malformations compatible with BPS phenotype. In order to identify the underlying genetic defect, direct sequencing of the coding region and exon-intron boundaries of RIPK4 was carried out. A homozygous transversion (c.481G>C) that leads to the substitution of a conserved aspartic acid to histidine (p.Asp161His) in the kinase domain of the protein was detected. Pathogenicity predictions, molecular modeling, and cell-based functional assays showed that Asp161 residue is required for the kinase activity of the protein, which indicates that the identified variant is responsible for the severe BPS phenotype in the family.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Anormalidades do Olho/genética , Dedos/anormalidades , Articulação do Joelho/anormalidades , Joelho/anormalidades , Deformidades Congênitas das Extremidades Inferiores/genética , Proteínas Serina-Treonina Quinases/genética , Anormalidades da Pele/genética , Sindactilia/genética , Anormalidades Urogenitais/genética , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Feto Abortado/patologia , Fenda Labial/epidemiologia , Fenda Labial/patologia , Fissura Palatina/epidemiologia , Fissura Palatina/patologia , Exoma/genética , Anormalidades do Olho/epidemiologia , Anormalidades do Olho/patologia , Feminino , Dedos/patologia , Predisposição Genética para Doença , Homozigoto , Humanos , Recém-Nascido , Joelho/patologia , Articulação do Joelho/patologia , Deformidades Congênitas das Extremidades Inferiores/epidemiologia , Deformidades Congênitas das Extremidades Inferiores/patologia , Mutação/genética , Fosforilação , Gravidez , Anormalidades da Pele/epidemiologia , Anormalidades da Pele/patologia , Sindactilia/epidemiologia , Sindactilia/patologia , Anormalidades Urogenitais/epidemiologia , Anormalidades Urogenitais/patologia
16.
J Orthop Surg (Hong Kong) ; 29(1): 23094990211002325, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33779392

RESUMO

When sizing the femoral component or determining its placement in total knee arthroplasty (TKA), if the anterior-posterior diameter of the femoral condyle is between component sizes, the selected size will differ depending on whether anterior referencing (AR) or posterior referencing (PR) is used. As a result, the amount of resected bone will also vary. In the present prospective study, we compared the two referencing methods to determine which is more suitable for individual patients. We recruited 58 patients (92 joints) who received TKA using the standard technique with intermediate-size components. AR was used in 26 joints, and PR in 23 joints. Seventeen of the patients underwent same-day bilateral TKA in which components of different sizes were used for the left and right joints. AR resulted in significantly smaller anterior and posterior offsets than PR. Preoperative clinical evaluation revealed no significant differences among cases in which intermediate-size components were indicated, or those in which components of different sizes were indicated. When an intermediate-sized component was indicated using the AR method, moving the sizer forward resulted in a larger posterior gap, but this technique was nevertheless considered acceptable. AR is likely to be more suitable than PR as it achieves more physiological anterior clearance.


Assuntos
Artroplastia do Joelho/métodos , Fêmur/cirurgia , Articulação do Joelho/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/normas , Feminino , Fêmur/patologia , Seguimentos , Humanos , Articulação do Joelho/patologia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Padrões de Referência
17.
Int J Sports Med ; 42(8): 682-693, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33784786

RESUMO

Although most studies have introduced risk factors related to anterior cruciate ligament reconstruction failure, studies on combinations of high-risk factors are rare. To provide a systematic review of the risk factors of anterior cruciate ligament reconstruction failure to guide surgeons through the decision-making process, an extensive literature search was performed of the Medline, Embase and Cochrane Library databases. Studies published between January 1, 2009, and September 19, 2019, regarding the existing evidence for risk factors of anterior cruciate ligament reconstruction failure or graft failure were included in this review. Study quality was evaluated with the quality index. Ultimately, 66 articles met our criteria. There were 46 cases classified as technical factors, 21 cases as patient-related risk factors, and 14 cases as status of the knee joint. Quality assessment scores ranged from 14 to 24. This systematic review provides a comprehensive summary of the risk factors for anterior cruciate ligament reconstruction failure, including technical factors, patient-related factors, and the factors associated with the status of the knee joint. Emphasis should be placed on avoiding these high-risk combinations or correcting modifiable risk factors during preoperative planning to reduce the rate of graft rupture and anterior cruciate ligament reconstruction failure.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Falha de Tratamento , Fatores Etários , Aloenxertos/anatomia & histologia , Reconstrução do Ligamento Cruzado Anterior/métodos , Autoenxertos/anatomia & histologia , Índice de Massa Corporal , Tomada de Decisão Clínica , Humanos , Articulação do Joelho/patologia , Osteotomia/métodos , Complicações Pós-Operatórias/etiologia , Volta ao Esporte , Fatores de Risco , Ruptura/etiologia , Ruptura/prevenção & controle , Tíbia , Lesões do Menisco Tibial/complicações , Suporte de Carga
18.
J Pediatr Orthop ; 41(6): e422-e426, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33782366

RESUMO

BACKGROUND: Current advanced imaging classification systems for osteochondritis dissecans (OCD) of the knee grade severity of disease by identifying certain lesion characteristics. The most widely used are the Hefti and Nelson systems. A novel classification presents a simpler 3-group approach to diagnose knee OCD by magnetic resonance imaging (MRI), compared with the Hefti (5-group) and Nelson (4-group) classifications. The purpose of this study was to compare the reliability of this novel classification with that of the more complex, established systems-an initial step in establishing validity and clinical utility. METHODS: In total, 120 standardized knee MRIs of patients with established knee OCD were preselected to capture the spectrum of lesion types, with regard to both progression and location of the lesion. Each of the MRIs were independently classified by 2 readers into the novel, Hefti, and Nelson classification systems. A random sample was rereviewed by 1 rater 6 weeks after initial review. The inter-rater and intrarater agreements were evaluated by estimating Krippendorff α. RESULTS: In total, 106 knees were classified by the novel, Hefti, and Nelson classification systems, as 14 of the knees lacked the necessary MRI sequences. There were no differences in inter-rater and intrarater agreement across classification systems. Krippendorff α for inter-rater agreement was 0.51 (95% confidence interval, 0.33-0.66) for the Hefti classification, 0.50 (0.34-0.64) for the Nelson classification, and 0.49 (0.32-0.65) for the novel classification. The intrarater agreement was 0.88 (0.75-0.97) for the Hefti classification, 0.94 (0.86-0.99) for the Nelson classification, and 0.98 (0.94-1.00) for the novel classification system. CONCLUSIONS: The novel classification for knee OCD demonstrated near-perfect intrarater agreement and moderate inter-rater agreement, consistent with the current, well-established classification systems. Pending a subsequent study on validity and clinical utility, this simpler classification system may offer an alternative, noninvasive diagnostic method to guide clinical treatment. LEVEL OF EVIDENCE: Level IV.


Assuntos
Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Osteocondrite Dissecante/diagnóstico por imagem , Índice de Gravidade de Doença , Humanos , Articulação do Joelho/patologia , Osteocondrite Dissecante/classificação , Reprodutibilidade dos Testes
19.
J Pediatr Orthop ; 41(6): e411-e416, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33782370

RESUMO

BACKGROUND: Osgood-Schlatter disease (OSD) and tibial tubercle fractures are pathologies that affect the tibial tubercle apophysis in preadolescents and adolescents. Anatomic alignment of the proximal tibia may explain why some children develop OSD or sustain tibial tubercle fractures and some do not. Recent data has shown an association between posterior tibial slope angle (PTSA) and both OSD and proximal tibia physeal fractures. In this study, we compare radiographic parameters between patients with non-OSD knee pain, knees with OSD, and knees with tibial tubercle fracture to elucidate a difference between these groups. METHODS: Patients treated for OSD, tibial tubercle fractures, and knee pain, from 2012 to 2018, were retrospectively reviewed. Radiographic parameters for each study group included PTSA, anatomic lateral distal femoral angle, anatomic medial proximal tibial angle, patellar articular height, and the distance from the inferior aspect of the patellar articular surface. Caton-Deschamps index was then calculated. Demographic data was collected including age, sex, and body mass index. Demographic and radiographic data was compared using analysis of variance tests, χ2 tests, 2-sample t tests, and multiple linear regression. RESULTS: Two hundred fifty-one knees in 229 patients met inclusion criteria for the study. In all, 76% were male and the average age of the overall cohort was 14 years old. In patients with tibial tubercle fractures, the majority of fractures were Ogden type 3b (65%). After controlling for demographic variability, average PTSA in the fracture cohort was significantly greater than that in the control cohort (ß=3.49, P<0.001). The OSD cohort had a significantly greater posterior slope (ß=3.14) than the control cohort (P<0.001). There was no statistically significant difference between the fracture and OSD cohorts. There was also no difference in Caton-Deschamps index between the 2 study groups when compared with the control group. CONCLUSION: This study demonstrates that patients with tibial tubercle fractures and patients with OSD have an increased PTSA when compared with the control group. This information adds to the body of evidence that increased tibial slope places the proximal tibial physis under abnormal stress which may contribute to the development of pathologic conditions of proximal tibia such as OSD and tibial tubercle fractures. LEVEL OF EVIDENCE: Level III; retrospective comparative study.


Assuntos
Articulação do Joelho/patologia , Osteocondrose/patologia , Tíbia/patologia , Fraturas da Tíbia/patologia , Adolescente , Estudos de Coortes , Feminino , Fêmur , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Osteocondrose/diagnóstico por imagem , Dor , Patela , Radiografia , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Fraturas da Tíbia/diagnóstico por imagem
20.
J Orthop Surg (Hong Kong) ; 29(1): 23094990211000462, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33745362

RESUMO

OBJECTIVES: To evaluate whether anthropometric data can predict anterior cruciate ligament (ACL) sizes on magneti resonance imaging (MRI) in Asian population. BACKGROUND: Reconstruction of ACL has been performed over a decade ago. Recently, more individualized ACL reconstruction is performed taking account of each patient's ACL characteristics. However, there has been limited study regarding ACL sizes in Asian Indonesian population. This study aimed to evaluate the role of anthropometric data in ACL sizes using MRI in Asian Indonesian population. STUDY DESIGN: Retrospective Study. METHOD: A series of 531 knees from 420 patients with knee pain and intact ACL confirmed by MRI study. Length, width and inclination angle of ACL were measured using a T2-weighted sagittal MRI 3.0 Tesla Magnetom Skyra. Height, weight, body mass index (BMI) and age were recorded. Multiple regression analysis was used to determine relationship between the anthropometric data and size of ACL measurements. RESULT: ACL length and width were significantly different between male and female, consecutively. Mean ACL length was 35.36 ± 3.63 mm, male was significantly longer (36.59 ± 3.24 mm) compared to female (32.77 ± 2.99 mm), p < 0.0001. Mean ACL width was 10.23 ± 1.84 mm, male was significantly wider (10.85 ± 1.59 mm) compared to female (8.93 ± 1.64 mm), p < 0.0001. The mean ACL inclination angle was 47.75° ± 3.07° (range 40.17°-57.12°). The strongest correlation for ACL length was height and weight (r = 0.437; r = 0.341 consecutively, p < 0.0001). Females had stronger correlation compared to males for ACL length (R2 = 0.489 vs R2 = 0.418). ACL width showed weak correlation with anthropometric data. The following regression analysis equation was obtained for ACL length: ACL length = 60.697 - 0.11*age + 0.461*weight (kg) - 16.522*height (meter) - 1.093*BMI (R2 = 0.539; p < 0.0001). CONCLUSION: Anthropometric data can be utilized as a predictor of ACL length in Asian Indonesian population. The ACL length in Asian Indonesian population is shorter than that in Western population study.


Assuntos
Ligamento Cruzado Anterior/anatomia & histologia , Pesos e Medidas Corporais , Adolescente , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/patologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Índice de Massa Corporal , Pesos e Medidas Corporais/estatística & dados numéricos , Feminino , Humanos , Indonésia/epidemiologia , Joelho/anatomia & histologia , Joelho/diagnóstico por imagem , Joelho/patologia , Articulação do Joelho/anatomia & histologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Adulto Jovem
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