RESUMEN
BACKGROUND: Osteoarthritis (OA) is a multifaceted condition that affects both the subchondral bones and the articular cartilage. Animal models are widely used as an effective supplement and simulation for human OA studies in investigating disease mechanisms and pathophysiology. This study is aimed to evaluate the temporal changes of bone and cartilage in surgically and chemically induced osteoarthritis using micro-computed tomography and histology. METHODS: Thirty rabbits underwent either anterior cruciate ligament transection (ACLT) procedure or injected intraarticularly with monosodium iodoacetate (MIA, 8 mg) at the right knee joint. The subchondral bones were scanned via micro-CT, and articular cartilage was assessed histologically at 4-, 8- and 12-week post-induction. RESULTS: Based on bone micro-architecture parameters, the surgically induced group revealed bone remodelling processes, indicated by increase bone volume, thickening of trabeculae, reduced trabecular separation and reduced porosity. On the other hand, the chemically induced group showed active bone resorption processes depicted by decrease bone volume, thinning of trabeculae, increased separation of trabecular and increased porosity consistently until week 12. Histologically, the chemically induced group showed more severe articular cartilage damage compared to the surgically induced group. CONCLUSIONS: It can be concluded that in the ACLT group, subchondral bone remodelling precedes articular cartilage damage and vice versa in the MIA group. The findings revealed distinct pathogenic pathways for both induction methods, providing insight into tailored therapeutic strategies, as well as disease progression and treatment outcomes monitoring.
Asunto(s)
Cartílago Articular , Osteoartritis , Animales , Ligamento Cruzado Anterior , Huesos , Cartílago Articular/diagnóstico por imagen , Modelos Animales de Enfermedad , Osteoartritis/inducido químicamente , Osteoartritis/diagnóstico por imagen , Conejos , Microtomografía por Rayos XRESUMEN
BACKGROUND: Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS: Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48â¯h, stimulated with interleukin-1ß (IL-1ß, 10â¯ng/mL) for 24â¯h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48â¯h after surgery and every 3â¯weeks thereafter: ACLT+Ad-GFP (nâ¯=â¯17); ACLT+Ad-HDAC4-GFP (nâ¯=â¯20); and sham+Ad-GFP (nâ¯=â¯15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. RESULTS: Overexpression of HDAC4 in chondrocytes stimulated by IL-1ß reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. CONCLUSION: HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.
Asunto(s)
Adenoviridae/genética , Histona Desacetilasas/genética , Osteoartritis , Animales , Cartílago Articular/metabolismo , Cartílago Articular/patología , Células Cultivadas , Condrocitos/metabolismo , Colágeno/genética , Colágeno/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Progresión de la Enfermedad , Interleucina-1beta/farmacología , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Masculino , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Ratas Sprague-Dawley , Transducción GenéticaRESUMEN
Objective To evaluate the combined diagnostic value of two serum osteoarthritis (OA) markers and quantitative magnetic resonance imaging (MRI) evaluation of the cartilage volume of the tibial plateau in a canine model of experimental OA. Methods A total of 18 male Beagle dogs were used in this longitudinal study. OA was surgically induced via anterior cruciate ligament transection (ACLT) of the right knee in 10 dogs. The remaining eight dogs formed the sham operation control group and underwent the same procedure without ACLT. At various times after surgery, enzyme-linked immunosorbent assay was used to measure serum C-telopeptide of type II collagen (CTX-II) and type X collagen (ColX) levels. Quantitative evaluation of the tibial plateau volume was undertaken using MRI and ImageJ software. Results The serum CTX-II levels were significantly higher in the OA group at weeks 8, 12 and 16 after surgery, but not at week 4, compared with the control group. The serum ColX levels in the OA group were significantly higher than in the control group at weeks 8 and 12. The tibial plateau cartilage volumes in the OA group were significantly lower than in the control group at weeks 8 and 16. Conclusion Serum CTX-II and ColX levels combined with quantitative MRI evaluation of the tibial plateau cartilage volume in a canine model of OA demonstrated the potential to detect and monitor OA progression.
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Biomarcadores/sangre , Cartílago Articular/patología , Imagen por Resonancia Magnética , Osteoartritis/sangre , Osteoartritis/cirugía , Tibia/patología , Animales , Cartílago Articular/diagnóstico por imagen , Colágeno Tipo I/sangre , Colágeno Tipo X/sangre , Modelos Animales de Enfermedad , Perros , Masculino , Tamaño de los Órganos , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Péptidos/sangre , Tibia/diagnóstico por imagenRESUMEN
Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren-Lawrence OA severity scores, the Kraus' modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.