scholarly journals Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats

2021 ◽  
Vol 22 (14) ◽  
pp. 7290
Author(s):  
Zhi-Hong Wen ◽  
Jhy-Shrian Huang ◽  
Yen-You Lin ◽  
Zhi-Kang Yao ◽  
Yu-Cheng Lai ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Histone Deacetylases ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Joint Inflammation ◽  
Cartilage Degeneration ◽  
Therapeutic Drug ◽  
Anterior Cruciate Ligament Transection ◽  
Chondrocyte Phenotype ◽  
Anterior Cruciate

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

scholarly journals Disturbances in Metabolic Pathways and the Identification of a Potential Biomarker Panel for Early Cartilage Degeneration in a Rabbit Anterior Cruciate Ligament Transection Model

Cartilage ◽  
2020 ◽  
pp. 194760352092143
Author(s):  
Yiwen Hu ◽  
Qian Wu ◽  
Yang Qiao ◽  
Peng Zhang ◽  
Wentao Dai ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Pearson Correlation ◽  
Rabbit Model ◽  
Cartilage Degeneration ◽  
Anterior Cruciate Ligament Transection ◽  
Sham Surgery ◽  
Potential Biomarker ◽  
Anterior Cruciate ◽  
Potential Biomarkers

Objective This study aimed to assess the association between synovial fluid (SF) metabolites and magnetic resonance imaging (MRI) measurements of cartilage biochemical composition to identify potential SF biomarkers for detecting the early onset of cartilage degeneration in a rabbit model. Methods Both knees of 12 New Zealand White rabbits were used. The anterior cruciate ligament transection (ACLT) model was performed on right knees, and the sham surgery on left knees. MRI UTE-T2* scanning and SF sample collection were performed on ACLT knees at 4 and 8 weeks postsurgery and on sham surgery knees at 4 weeks postsurgery. Ultra-performance liquid chromatography–mass spectrometry and multivariate statistical analysis were used to distinguish samples in three groups. Pathway and receiver operating characteristic analyses were utilized to identify potential metabolite biomarkers. Results There were 12 knees in sham surgery models, 11 in ACLT models at 4 weeks postsurgery, and 10 in ACLT models at 8 weeks postsurgery. UTE-T2* values for the lateral tibia cartilage showed significant decreases over the study period. Levels of 103 identified metabolites in SF were markedly different among three groups. Furthermore, 24 metabolites were inversely correlated with UTE-T2* values of the lateral tibia cartilage, while hippuric acid was positively correlated with UTE-T2* values of the lateral tibia cartilage. Among 25 potential markers, N1-acetylspermidine, 2-amino-1,3,4-octadecanetriol, l-phenylalanine, 5-hydroxy-l-tryptophan, and l-tryptophan were identified as potential biomarkers with high area under the curve values and Pearson correlation coefficients. Conclusion Five differential metabolites in SF were found as potential biomarkers for the early detection of cartilage degeneration in the rabbit ACLT model.

scholarly journals Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats

2018 ◽  
Author(s):  
Sabri Sudirman ◽  
Alan Darmasaputra Ong ◽  
Heng-Wei Chang ◽  
Zwe-Ling Kong
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cholesterol Level ◽  
High Fat Diet ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Hdl Cholesterol ◽  
High Fat ◽  
Anterior Cruciate Ligament Transection ◽  
Medial Meniscectomy ◽  
Anterior Cruciate

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in female. Obesity and mechanical injury causing OA are attributed to joint loading, cartilage disintegration, bone loss and inflammation as well. Several strategies used for treatment OA including non-pharmacological and pharmacological. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on diet-induced obesity rats. OA was induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT+MMx). Male SD rats were fed high-fat diet (HFD) for 4 weeks to induce obesity before ACLT+MMx to induce OA. OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with HFD. We observed that the swelling in knee joint was alleviated and hind paw weight distribution was rectified after feeding fucoidan, with no significant effect on weight gain and feed intake. Fucoidan administration indicated no significant variation on HDL-Cholesterol level, but reduced plasma triglycerides and LDL-Cholesterol level. In addition, weight-bearing tests showed improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

scholarly journals Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats

2018 ◽  
Author(s):  
Sabri Sudirman ◽  
Alan Darmasaputra Ong ◽  
Heng-Wei Chang ◽  
Zwe-Ling Kong
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cholesterol Level ◽  
High Fat Diet ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Hdl Cholesterol ◽  
High Fat ◽  
Anterior Cruciate Ligament Transection ◽  
Medial Meniscectomy ◽  
Anterior Cruciate

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in female. Obesity and mechanical injury causing OA are attributed to joint loading, cartilage disintegration, bone loss and inflammation as well. Several strategies used for treatment OA including non-pharmacological and pharmacological. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on diet-induced obesity rats. OA was induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT+MMx). Male SD rats were fed high-fat diet (HFD) for 4 weeks to induce obesity before ACLT+MMx to induce OA. OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with HFD. We observed that the swelling in knee joint was alleviated and hind paw weight distribution was rectified after feeding fucoidan, with no significant effect on weight gain and feed intake. Fucoidan administration indicated no significant variation on HDL-Cholesterol level, but reduced plasma triglycerides and LDL-Cholesterol level. In addition, weight-bearing tests showed improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

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