RESUMO
Osteoarthritis (OA) is a heterogeneous condition characterized by cartilage degradation, subchondral sclerosis, and osteophyte formation, and accompanied by the generation of pro-inflammatory mediators and degradation of extracellular matrix. The current treatment for early OA is focused on the relief of symptoms, such as pain, but this treatment cannot delay the pathological process. L-Glutamine (L-Gln), which has anti-inflammatory and anti-apoptotic effects, is the most abundant amino acid in human blood. However, its role in OA has not been systematically studied. Therefore, the objective of this work was to explore the therapeutic effect and molecular mechanism of L-Gln on OA. In vitro, we found that L-Gln could up-regulate the expression of the long non-coding RNA NKILA, which is regulated by the transforming growth factor-ß1/SMAD2/3 pathway, and inhibit the activity of nuclear factor-κB, thereby decreasing the expression of nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-13 (MMP-13). This led to a reduction in the generation of nitrous oxide, prostaglandin E-2, tumour necrosis factor-α, and degradation of the extracellular matrix (i.e. aggrecan and collagen II) in rat OA chondrocytes. Moreover, intragastric administration of L-Gln reduced the degradation of cartilage tissue and expression of MMP-13 in a rat OA model. L-Gln also relieved the clinical symptoms in some patients with early knee joint OA. These findings highlight that L-Gln is a potential therapeutic drug to delay the occurrence and development of OA.
Assuntos
Glutamina , Osteoartrite do Joelho , RNA Longo não Codificante , Proteína Smad2 , Proteína Smad3 , Fator de Crescimento Transformador beta1 , Animais , Condrócitos/metabolismo , Condrócitos/patologia , Glutamina/metabolismo , Glutamina/farmacologia , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ratos , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
[This corrects the article DOI: 10.3389/fsurg.2022.885669.].
RESUMO
[This corrects the article DOI: 10.3389/fsurg.2022.885669.].
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Titanium dioxide (TiO2) nanotubes can improve the osseointegration of pure titanium implants, but this exact mechanism has not been fully elucidated. The purinergic receptor P2Y6 is expressed in bone marrow mesenchymal stem cells (BMSCs) and participates in the regulation of bone metabolism. However, it is unclear as to whether P2Y6 is involved in the osteogenic differentiation of BMSCs induced by TiO2 nanotubes. TiO2 nanotubes were prepared on the surface of titanium specimens using the anodizing method and characterized their features. Quantitative reverse transcriptase polymerase chain reaction and western blotting were used to detect the expression of P2Y6, markers of osteogenic differentiation, and PKCα-ERK1/2. A rat femoral defect model was established to evaluate the osseointegration effect of TiO2 nanotubes combined with P2Y6 agonists. The results showed that the average inner diameter of the TiO2 nanotubes increased with an increase in voltage (voltage range of 30-90V), and the expression of P2Y6 in BMSCs could be upregulated by TiO2 nanotubes in osteogenic culture. Inhibition of P2Y6 expression partially inhibited the osteogenic effect of TiO2 nanotubes and downregulated the activity of the PKCα-ERK1/2 pathway. When using in vitro and in vivo experiments, the osteogenic effect of TiO2 nanotubes when combined with P2Y6 agonists was more pronounced. TiO2 nanotubes promoted the P2Y6 expression of BMSCs during osteogenic differentiation and promoted osteogenesis by activating the PKCα-ERK1/2 pathway. The combined application of TiO2 nanotubes and P2Y6 agonists may be an effective new strategy to improve the osseointegration of titanium implants. STATEMENT OF SIGNIFICANCE: Titanium dioxide (TiO2) nanotubes can improve the osseointegration of pure titanium implants, but this exact mechanism has not been fully elucidated. The purinergic receptor P2Y6 is expressed in bone marrow mesenchymal stem cells (BMSCs) and participates in the regulation of bone metabolism. However, it is unclear as to whether P2Y6 is involved in the osteogenic differentiation of BMSCs induced by TiO2 nanotubes. For the first time, this study revealed the relationship between TiO2 nanotubes and purine receptor P2Y6, and further explored its mode of action, which may provide clues as to the regulatory role of TiO2 nanotubes on osteogenic differentiation of BMSCs. These findings will help to develop novel methods for guiding material design and biosafety evaluation of nano implants.
Assuntos
Células-Tronco Mesenquimais , Nanotubos , Ratos , Animais , Osteogênese , Titânio/farmacologia , Sistema de Sinalização das MAP Quinases , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-alfa/farmacologia , Diferenciação Celular , Células da Medula Óssea , Células CultivadasRESUMO
Objective: The study aims to explore the feasibility and clinical effect of posterior minimally invasive treatment of cruciate ligament tibial avulsion fracture. Methods: Posterior knee minimally invasive approach was used to treat avulsion fracture of posterior cruciate ligament (PCL) tibia in 15 males and 11 females. The length of the incision, intraoperative blood loss, operation time, postoperative hospital stay, residual relaxation, and fracture healing time were analyzed to evaluate the curative effect, learning curve, and advantages of the new technology. Neurovascular complications were recorded. During the postoperative follow-up, the International Knee Joint Documentation Committee (IKDC), Lysholm knee joint score, and knee joint range of motion were recorded to evaluate the function. Results: All 26 patients were followed up for 18-24 months, with an average of 24.42 ± 5.00 months. The incision length was 3-6 cm, with an average of 4.04 ± 0.82â cm. The intraoperative blood loss was about 45-60â ml, with an average of 48.85 ± 5.88â ml. The operation time was 39-64â min, with an average of 52.46 ± 7.64 min. The postoperative hospital stay was 2-5 days, with an average of 2.73 ± 0.87 days. All incisions healed grade I without neurovascular injury. All fractures healed well with an average healing time of 9.46 ± 1.33 weeks (range, 8-12 weeks). The Lysholm score of the affected knee was 89-98 (mean, 94.12 ± 2.49) at 12-month follow-up. The IKDC score was 87-95 with an average of 91.85 ± 2.19, and the knee range of motion was 129-148° with an average of 137.08 ± 5.59°. The residual relaxation was 1-3â mm, with an average of 1.46 ± 0.65â mm. Conclusion: This minimally invasive method provides sufficient exposure for internal fixation of PCL tibial avulsion fractures without the surgical complications associated with traditional open surgical methods. The process is safe, less invasive, and does not require a long learning curve.