RESUMO
BACKGROUND: It has been demonstrated that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic knee osteoarthritis (PTKOA).Pituitary adenylate cyclase-activating polypeptide (PACAP), a common neuropeptide exerting a wide spectrum of functions, has been proved to inhibit inflammation and prevent cartilage degeneration. OBJECTIVE: The current study was performed to investigate circulating and synovial fluid PACAP concentrations in ACL injury patients to determine their relationship with the disease progression of the severity of post-traumatic knee osteoarthritis (PTKOA). METHODS: 72 ACL injury patients receiving arthroscopical examination and surgery were enrolled in the study. Meanwhile, 60 gender-and-age non-traumatic patellar dislocation patients were enrolled as controls. The VAS score, Lysholm Score and International Knee Documentation Committee (IKDC) score were all recorded to evaluate the clinical severity. Serum and synovial fluid (SF) PACAP levels were investigated by enzyme-linked immunosorbent assay (ELISA).The IL-1ß and TNF-α levels were also investigated. The degree of meniscus injury was assessed by MR imaging. The modified Mankin score was recorded to examine the cartilage histopathological alternations. Receiver operating characteristic (ROC) curve was performed to discuss the diagnostic value of PACAP levels for the prediction of the radiographic grading in comparison with IL-1ß and TNF-α. RESULTS: Serum PACAP levels between PTKOA patients and patellar dislocation did not reach significant differences. However, SF PACAP levels were significantly lower in PTKOA patients than controls. In addition, SF PACAP levels were negatively associated with MRI imaging grade for meniscus injury and VAS score, and were positively associated with Lysholm and IKDC scores. In addition, SF PACAP levels were negatively related to Mankin score as well as the expressions of IL-1ß and TNF-α. ROC analysis curve showed that attenuated PACAP may serve as a favorable marker for the diagnosis of MRI for meniscus injury. CONCLUSIONS: SF PACAP concentrations showed an independent and negative association with disease severity in PTKOA following ACL injury. Local treatment with PACAP may act as a possible adjuvant therapy for delaying the process of PTKOA.
Assuntos
Lesões do Ligamento Cruzado Anterior/metabolismo , Osteoartrite do Joelho/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Líquido Sinovial/metabolismo , Adulto , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/diagnóstico , Lesões do Ligamento Cruzado Anterior/patologia , Biomarcadores/metabolismo , Cartilagem/metabolismo , Cartilagem/patologia , Feminino , Humanos , Interleucina-1beta/metabolismo , Masculino , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
The correlation of serum and synovial fluid (SF) pituitary adenylate cyclase-activating polypeptide (PACAP) levels with disease progression of primary knee osteoarthritis (OA) was explored. Radiographic severity of OA was determined by Kellgren-Lawrence (K-L) grades. PACAP levels were measured by ELISA before treatment, and 4 and 8 wk following hyaluronic acid (HA) injection. Levels of IL-1ß and MMP-3 were also detected. The numeric pain scale (NPS), revised Oxford Knee Score (OKS), and American Knee Society Score (AKSS) were employed to evaluate to symptomatic severity. Receiver-operating-characteristic (ROC) curve analysis was carried out to compare the diagnostic value of PACAP, IL-1ß, and MMP-3 for the K-L grade. PACAP concentrations in SF but not serum were significantly lower in OA patients compared with controls. SF PACAP levels were negatively associated with K-L grades and higher NPS as well as worse AKSS and OKS. Further analysis demonstrated that PACAP concentration in SF was negatively correlated with expressions of IL-1ß as well as MMP-3 and may act as a marker for radiographic progression along with MMP-3. Last, we found SF PACAP levels exhibited an incremental trend after HA injection. These findings confirmed the crucial role of PACAP deficiency in the development of primary knee OA.
Assuntos
Cartilagem Articular/diagnóstico por imagem , Fármacos Neuroprotetores/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Líquido Sinovial/metabolismo , Sinoviócitos/metabolismo , Progressão da Doença , Feminino , Humanos , Ácido Hialurônico/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Osteoartrite do JoelhoRESUMO
Bone defects represent a major clinical and socioeconomic problem without suitable treatment options. Previous studies have shown that transforming growth factor ß1 (TGFß1) is important in the development of various diseases. The present study aimed to investigate the therapeutic potential of rabbit bone marrowderived mesenchymal stem cells (BMSCs) expressing TGFß1 in the treatment of rabbit femoral defects. First, rabbit BMSCs were identified and cultured. TGFß1 was then stably overexpressed in the rabbit BMSCs by lentivirus transfection, which was expressed at a high level in the femoral defects treated with TGFß1overexpressing BMSCs, compared with PBStreated controls. In addition, the TGFß1overexpressing BMSCs promoted new bone formation in the rabbit femoral defect model, and increased the expression of bonerelated markers at week 2 and week 6. Therefore, the study demonstrated that BMSCs overexpressing TGFß1 may provide a novel therapeutic option for femoral defects.
Assuntos
Fêmur/lesões , Transplante de Células-Tronco Mesenquimais , Osteogênese , Fator de Crescimento Transformador beta1/genética , Regulação para Cima , Animais , Células Cultivadas , Fêmur/fisiologia , Fêmur/fisiopatologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , CoelhosRESUMO
Great variations have been found in composition and content of the essential oil of Zanthoxylum bungeanum Maxim. (Rutaceae), resulting from various factors such as harvest time, drying and extraction methods (Huang et al., 2006; Shao et al., 2013), solvent and herbal parts used (Zhang, 1996; Cao and Zhang, 2010; Wang et al., 2011). However, in terms of artificial introduction and cultivation, there is little research on the chemical composition of essential oil extracted from Z. bungeanum Maxim. cultivars, which have been introduced from different origins. In this study, the composition and content of essential oil from six cultivars (I-VI) have been investigated. They were introduced and cultivated for 11 years in the same cultivation conditions. Cultivars were as followings: Qin'an (I) cultivar originally introduced from Qin'an City in Gansu Province; Dahongpao A (II) from She County in Hebei Province; Dahongpao B (III) from Fuping County; Dahongpao C (IV) from Tongchuan City; Meifengjiao (V) from Feng County; and, Shizitou (VI) from Hancheng City, in Shaanxi Province, China. This research is expected to provide a theoretical basis for further introduction, cultivation, and commercial development of Z. bungeanum Maxim.