Development of a rat model of knee osteoarthritis by a combination of monoiodoacetate and streptozotocin / Desarrollo de un modelo de rata de osteoartritis de rodilla por una combinación de monoiodoacetato y estreptozotocina

SUMMARY: Osteoarthritis (OA) caused by ageing joints or as a secondary complication of diabetes is a common health problem. We sought to develop an animal model of OA induced by a combination of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA) and streptozotocin (STZ), the agent that induces diabetes mellitus. We then hypothesized that the extent of damages to the knee joint induced by this model can be greater than OA induced by either MIA or STZ. Rats were either injected with MIA (model 1) or STZ (model 2) or both agents (model 3). After 8 weeks, harvested tissues from the knee joint of these groups were examined using scanning and transmission electron microscopy. In addition, blood samples were assayed for tumor necrosis factor alpha (TNF-α) and interleukin -6 (IL-6) that are known to be modulated in OA and diabetes. Compared to control group, substantial damages to the articular cartilage of the knee joint were observed in the three models with the severest in model 3. In addition, rats in model 3 showed significant (P<0.0001) increase in TNF-α and IL-6 compared to model 1 and 2. Thus, we have developed a new model of knee OA in rats that mimics a type of OA that is common among elderly people who have both, "ageing" joints and diabetes.

RESUMEN: La osteoartritis (OA) es un problema generalizado de salud a causa de un envejecimiento de las articulaciones, o bien de una complicación secundaria de la diabetes. El objetivo de este estudio fue desarrollar un modelo animal de OA inducido por una combinación dos drogas, un inhibidor de los condrocitos glucolíticos, el mono-iodoacetato (MIA), y la estreptozotocina (STZ), agente que induce la diabetes mellitus. Se consideró como hipótesis que el alcance de los daños a la articulación de la rodilla inducida por este modelo puede ser mayor que la OA inducida por MIA o STZ. Las ratas fueron inyectadas con MIA (grupo 1) o STZ (grupo 2) o ambos agentes (grupo 3). Se extrajeron muestras de la articulación de la rodilla de estos grupos al término de 8 semanas, y se examinaron mediante microscopía electrónica de barrido y de transmisión. Además, se analizaron muestras de sangre para el factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6), que están moduladas en OA y en la diabetes. En comparación con el grupo control, se observaron daños sustanciales en el cartílago articular de la articulación de la rodilla en los tres modelos, encontrándose los daños más severos en el grupo 3. Además, las ratas del grupo 3 mostraron un aumento significativo (P <0,0001) de los niveles de TNF-α e IL- 6, en comparación con los grupos 1 y 2. Hemos desarrollado un nuevo modelo de OA de rodilla en ratas que imita un tipo de OA el cual, además de la diabetes, es común entre las personas mayores con un nivel importante de daño en las articulaciones.

Isolation and characterization of calcium phosphate crystals in the human articular knee cartilages and intervertebral discs: an electron microscopic study

The multiple complains of pain resulting from intervertebral disc prolapse or osteoarthritic knee joint is one of the most significant neurosurgical and orthopaedic disorders in industrialized society. The exact relationship between calcium phosphate crystal deposition and these diseases remains obscure, although there is evidence supporting a rapid degenerative arthropathy within a specific set of patients. Several basic calcium phosphate crystals have been reported to be associated with osteoarthritis joint diseases as well as in lumbar disc prolapse patients. To compare the presence and characters of calcium phosphate crystals in normal and osteoarthritic human articular knee cartilages as well as in degenerated disc patients. Five normal articular knee cartilages and intervertebral discs were taken from human cadavers at the dissection room, Faculty of Medicine, Taibah University. Osteoarthritic articular cartilage, and disc prolapse, fifteen specimens each, were obtained from Saudi German, Madinah National Hospitals; and Alexandria University Hospital respectively. Specimens were examined by light and electron microscopy, and electron probe x-ray microanalysis. No crystals could be detected at the light microscopic level. By electron microscopy, crystals were detected in cartilages from all pathological sites sampled. Few or no crystals were observed in normal articular knee cartilages and intervertebral discs. Coexistence of calcium pyrophosphate dihydrate and cuboid calcium phosphate crystals was seen in all cases. Identification was based on the distinctive morphology, size range and XRMA spectrum. The results of this research confirmed the density of calcium phosphate and pyrophosphate dehydrate crystals in osteoarthritic cartilage, and degenerated disc that may provide a useful diagnostic and therapeutic approach to osteoarthritis and disc prolapse patients

Cartílago normal y patológico / Normal and pathological articular cartilage

El cartílago articular es el tejido responsable de la lubricación y rigidez compresiva de las articulaciones durante el movimiento, gracias a sus propiedades de viscoelasticidad a la carga mecánica. Sin embargo, una vez dañado tiene una capacidad limitada o mínima de curación y a menudo evoluciona a cambios patológicos degenerativos. Debido a lo anterior se hace necesario revisar las ciencias básicas para comprender mejor el rol que éste cartílago articular juega durante éste proceso reparativo. Este artículo fue escrito en un esfuerzo para mejorar nuestra comprensión del proceso curativo del cartílago articular