RESUMEN
This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.
Asunto(s)
Artritis Experimental/complicaciones , Artritis Reumatoide/complicaciones , Osteoporosis/etiología , Animales , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/fisiopatología , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/fisiopatología , Fenómenos Biomecánicos , Densidad Ósea/fisiología , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/etiología , Resorción Ósea/fisiopatología , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Fémur/fisiopatología , Ratones Endogámicos BALB C , Ratones Mutantes , Osteoporosis/diagnóstico por imagen , Osteoporosis/patología , Osteoporosis/fisiopatología , Ovariectomía , Índice de Severidad de la Enfermedad , Microtomografía por Rayos XRESUMEN
OBJECTIVES: We hypothesized that high-molecular-weight (MW) cross-linked (CL) hyaluronic acid (HA) improves joint lubrication and has an enhanced chondroprotective effect. We examined the histopathological changes and friction coefficients in osteoarthritic knee joints after injecting high-MW CL HA. DESIGN: A bilateral anterior cruciate ligament transection (ACLT) model in 20 Japanese white rabbits was used. From week 5 after transection, low-MW HA (0.8 × 10(6) Da; HA80) or high-MW CL HA (6 × 10(6) Da; HA600) was injected weekly into 10 right knee for 3 weeks; normal saline (NS) was injected into the 10 left knee. A sham operation was undertaken to exclude spontaneous osteoarthritis (OA) in five knees. Results were evaluated with macroscopy, histopathology (Kikuchi's score), biomechanical testing, and rheological assessment of the joint fluid viscoelasticity. Statistical analysis was performed using one-way analysis of variance with a 95% confidence interval (CI) (P < 0.05). RESULTS: The macroscopic findings showed severely damaged cartilage in 30% of the NS group and 20% of the HA80 and HA600 groups and intact cartilage in 100% of the sham group. The histological scores and friction coefficients of the HA600 group were significantly lower than those of the NS group (P = 0.007 and P = 0.002, respectively). Viscoelasticity measurements of the joint fluid showed no significant differences between the three treatment groups. CONCLUSION: High-MW CL HA exerts potential chondroprotective effects and produces superior friction coefficients. Our results suggest that HA600 delays the progression of OA effectively and improves joint lubrication significantly.
Asunto(s)
Artritis Experimental/prevención & control , Cartílago Articular/patología , Ácido Hialurónico/uso terapéutico , Osteoartritis de la Rodilla/prevención & control , Viscosuplementos/uso terapéutico , Animales , Lesiones del Ligamento Cruzado Anterior , Artritis Experimental/patología , Artritis Experimental/fisiopatología , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Elasticidad , Femenino , Fémur/patología , Fricción , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/química , Inyecciones Intraarticulares , Lubrificación/métodos , Peso Molecular , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Conejos , Líquido Sinovial/fisiología , Viscosidad , Viscosuplementación/métodos , Viscosuplementos/administración & dosificación , Viscosuplementos/químicaRESUMEN
In synovial joints, friction between articular surfaces leads to shear stress within the cartilaginous tissue, which might result in tissue rupture and failure. Joint friction depends on synovial lubrication of the articular surfaces, which can be altered due to compressive loading. Therefore, we hypothesized that the frictional coefficient of the temporomandibular joint (TMJ) is affected by the magnitude and duration of loading. We tested this by measuring the frictional coefficient in 20 intact porcine TMJs using a pendulum-type friction tester. The mean frictional coefficient was 0.0145 (SD 0.0027) after a constant loading of 50 N during 5 sec. The frictional coefficient increased with the length of the preceding loading duration and exceeded 0.0220 (SD 0.0014) after 1 hr. Application of larger loading (80 N) resulted in significantly larger frictional coefficients. In conclusion, the frictional coefficient in the TMJ was proportional to the magnitude and duration of joint loading.
Asunto(s)
Articulación Temporomandibular/fisiología , Algoritmos , Análisis de Varianza , Animales , Cartílago Articular/fisiología , Fricción , Rotación , Estrés Mecánico , Porcinos , Líquido Sinovial/fisiología , Membrana Sinovial/fisiología , Factores de Tiempo , Soporte de Peso/fisiologíaRESUMEN
The purpose of this study was to test the hypothesis that exchange transfusion with liposomal hemoglobin (LH) reduces the microheterogeneity of regional myocardial flows while sustaining cardiac function. Neo Red Cell mixed with albumin was used as the LH solution, in which the LH volume fraction was 17 approximately 18% and hemoglobin density was nearly two-thirds smaller than in rat blood. Regional myocardial flows in left ventricular free walls were measured by tracer digitalradiography (100-mum resolution) in anesthetized rats with or without 50% blood-LH exchange transfusion. Within-layer flow distributions showed lower heterogeneity with (n = 8) than without (n = 8) LH transfusion. No extravasation of hemoglobin was confirmed by 3,3-diaminobenzidin staining (n = 2). Carotid flow increased by 68% due to LH transfusion, whereas arterial pressure and heart rate remained unchanged. On the other hand, cross-circulated rat hearts (n = 7) were used to evaluate the effects of 50% blood-LH exchange on coronary flow and tone preservation under 300-beats/min pacing and 100-mmHg perfusion pressure. Blood-LH exchange caused a 71% increase of coronary flow and 10% decrease of percent flow increase during hyperemia after 30-s flow interruption. Myocardial O(2) supply and consumption increased by 9% and 10%, respectively, whereas myocardial O(2) extraction remained unchanged. The large increases of in vivo carotid flow and coronary flow in cross-circulated hearts due to LH coperfusion could be explained by the reduction of apparent flow viscosity. These results suggest that under LH coperfusion, the microheterogeneity of myocardial flows decreases with increased coronary flow while fairly preserving coronary tone and cardiac function.