scholarly journals Serum amyloid A 1 protein isoforms induce Rheumatoid Arthritis

2020 ◽  
Author(s):  
Elaine Lai-Han Leung ◽  
Huan-Ling Lai ◽  
Run-Ze Li ◽  
Hu-Dan Pan ◽  
Ze-Bo Jiang ◽  
...  

Abstract Background: SAA1 in RA pathogenesis and its complications remains unknown, making early diagnosis and risk prevention difficult. This study is to determine the pathogenetic mechanisms of three different SAA1 protein isoforms in RA progression. Methods: We modified an experimental adenovirus infection protocol in order to successfully introduce SAA1.2, SAA1.3, SAA1.5 gene alleles into the rear knee joints of C57BL/6 mice. Micro-computed tomography (micro-CT) analysis was applied to determine changes in bone morphology and density. Immunohistochemistry (IHC), flow cytometry, ELISA and real-time PCR were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction. Results: The pathogenetic functions of SAA1.2, SAA1.3 and SAA1.5 protein isoforms in promoting the initiation and progression of RA were determined. We established that SAA1.2 was the most aggressive factor in RA induction and progression. Mechanistically, we found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood results in stimulation of immune responses, leading to CD8+ T cell and pro-inflammatory cytokine elevation, with subsequent synovial inflammation and bone destruction. Conclusions: These findings indicate that SAA1 protein isoforms, particularly SAA1.2, play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction for RA.

2016 ◽  
Vol 78 (6-8) ◽  
Author(s):  
Khairunnisa Abd Manan ◽  
Sulaiman Md Dom

The established of micro computed tomography (micro-CT) analysis software make it compatible to use to determine abnormality of bone morphology. This study investigated 90 new rabbits for bony trabecular microstructure and porosity after their dams were exposed to ultrasound at the second stage of pregnancy (duration - 90 minutes; frequency - 7.09 MHz; spatial peak temporal average intensity (SPTA) - 49.4 W/cm2; power - 56 W; thermal index (TI) - 0.2; mechanical index (MI) - 1.0). A femur of five groups of litters (n = 18 litters per group): 1, 2, 3, 4 and 5 month-old was excised and scanned using SkyscanTM 1176. For total porosity, a significant difference was shown in at two month-old group (p = 0.017). A significant difference was also shown in bony trabecular thickness for three month-old group (p < 0.05). For trabecular separation, there was a significant difference at four month-old group (p = 0.040). This study suggested that there might be some significant differences in bony trabecular structure and total porosity with ages. This may be due to heat created by ultrasound exposure, which can apply effect to bone morphology. To determine whether the findings are applicable to human, clinical trials should be carried out in the future.


2009 ◽  
Vol 36 (4) ◽  
pp. 684-692 ◽  
Author(s):  
JUN-HEE LEE ◽  
MI-LA CHO ◽  
JU-IN KIM ◽  
YOUNG-MEE MOON ◽  
HYE-JWA OH ◽  
...  

Objective.To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.Methods.On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR.Results.In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6.Conclusion.IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.


Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 1995
Author(s):  
Mirko Sinico ◽  
Suraj Dinkar Jadhav ◽  
Ann Witvrouw ◽  
Kim Vanmeensel ◽  
Wim Dewulf

Recently, the use of novel CuCr1 surface-modified powder for reliable laser powder-bed fusion (LPBF) manufacturing has been proposed, enabling a broader LPBF processing window and longer powder storage life. Nevertheless, virgin CuCr1 powder is also LPBF processable, on the condition that a high-energy density is employed. In this work, we compare two dense specimens produced from virgin and surface-modified CuCr1 powder. Furthermore, a third sample fabricated from surface-modified powder is characterized to understand an abnormal porosity content initially detected through Archimedes testing. Utilizing high-resolution micro-CT scans, the nature of the defects present in the different samples is revealed. Pores are analyzed in terms of size, morphology and spatial distribution. The micro-CT data reveal that the virgin CuCr1 dense specimen displays keyhole pores plus pit cavities spanning multiple layer thicknesses. On the other hand, the sample fabricated with the surface-modified CuCr1 powder mainly contains small and spherical equi-distributed metallurgical defects. Finally, the CT analysis of the third specimen reveals the presence of a W contamination, favoring lack-of-fusion pores between subsequent LPBF layers. The LPBF melting mode (keyhole or conductive), the properties of the material, and the potential presence of contaminants are connected to the different porosity types and discussed.


2021 ◽  
Author(s):  
Vadood Javadi Parvaneh ◽  
Khosro Rahmani

Juvenile idiopathic arthritis (JIA) is the most common form of chronic synovial joint inflammation in children. It potentially leads to disability and psychosocial outcomes for children and their families. In the absence of appropriate treatment, this can lead to joint destruction and disability. Thus, early diagnosis and aggressive treatment are essential. With the presentation of new biologic DMARDs, based on understanding the disease pathophysiology and molecular pathogenesis, the course of the disease and its outcome have been changed profoundly. In this chapter, the early diagnosis, appropriate treatment, and outcomes approaches are described. These include the latest diagnosis and management options.


2010 ◽  
Vol 37 (3) ◽  
pp. 212-216 ◽  
Author(s):  
N. D. COHEN ◽  
M. K. CHAFFIN ◽  
M. L. VANDENPLAS ◽  
R. F. EDWARDS ◽  
M. NEVILL ◽  
...  

2021 ◽  
pp. 002199832110338
Author(s):  
Elisson BD da Rocha ◽  
Ana Maria F de Sousa ◽  
Ana Lúcia N da Silva ◽  
Cristina RG Furtado ◽  
Marcos V Colaço ◽  
...  

This study reports the reinforcement degree investigation of two types of rockwool fibers (F1 and F2), in nitrile rubber composites. The micro-computed tomography (micro-CT) 3D images showed that both fibers were well-dispersed in the NBR matrix, without a preferential orientation. The micro-CT analysis also allowed quantifying volume fraction, inter-fiber distance, and aspect ratio. Those morphometric parameters were used for supporting the composites rheological behavior assessment. Changes in the elastic modulus and phase angle followed the same trend of the inter-fiber distance values, regardless the type of fiber. Both volume fraction and aspect ratio data from the micro-CT analysis were used to predict theoretical values of elastic modulus using the Guth-Gold and modified Guth-Gold equations, and the results obtained were compared to the rheological experimental data. This analysis was helpful to better understand the rockwool fibers reinforcement degree differences in the production of the nitrile rubber composites.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hua Cui ◽  
Haiyang Shu ◽  
Dancai Fan ◽  
Xinyu Wang ◽  
Ning Zhao ◽  
...  

Wang-Bi Capsule (WB), a traditional Chinese medicine- (TCM-) based herbal formula, is currently used in clinic for the treatment of rheumatoid arthritis (RA) with positive clinical effects. However, its pharmacological mechanism of action in RA is still obscure. Therefore, this study established a collagen-induced arthritis (CIA) mice model to examine the efficacy of WB by using arthritis score, histological analysis, and micro-CT examination. Proinflammatory cytokines expression, osteoclast number, OPG/RANKL system, and NF-κB activation were then detected to further investigate the mechanism of WB in RA treatment. The results indicated that WB could alleviate the erythema and swelling of paws in CIA mice. It also inhibited the infiltration of inflammatory cells and bone destruction and increased bone density in joints of CIA mice. Mechanistic studies showed that WB treatment decreased the production of IL-1β, IL-6, and TNF-α in serum and joints of CIA mice. Moreover, it reduced the osteoclast number, increased OPG level, decreased RANKL level, and inhibited the activation of NF-κB in joints of CIA mice. In conclusion, this study demonstrated that WB could effectively alleviate disease progression of CIA mice by decreasing the IL-1β, IL-6, and TNF-α levels, modulating the OPG/RANKL system, and inhibiting the activation of NF-κB.


Materials ◽  
2020 ◽  
Vol 13 (21) ◽  
pp. 4748
Author(s):  
Ulrike Kuchler ◽  
Patrick Heimel ◽  
Alexandra Stähli ◽  
Franz Josef Strauss ◽  
Bernadette Luza ◽  
...  

Deproteinized bovine bone mineral (DBBM) is brittle and can break into fragments. Here, we examined whether DBBM fragments have an impact on mice calvarial bone during bone augmentation. DBBM was either randomly crushed (DBBM fragments) or left undisturbed (DBBM granules). Then, DBBM fragments or original DBBM granules were placed onto calvarial bone in 20 BALB/c mice. Following random allocation, ten mice received DBBM fragments and ten mice received original DBBM granules. After fourteen days of healing, micro computed tomography (micro-CT) and histological analysis of the augmented sites were performed. The primary outcome was the porosity of the calvarial bone. The micro-CT analysis revealed that DBBM fragments failed to significantly change the porosity of the calvarial bone as compared with original DBBM granules, despite the slightly higher bone resorption in the DBBM fragment group, 10.3% (CI 6.3–11.6) versus 6.1% (CI 4.1–7.8, p = 0.355), respectively. The cortical bone volume was not altered by DBBM fragments as compared with original DBBM granules, i.e., 79.0% (CI 78.9–81.2) versus 81.5% (CI 80.1–83.3, p = 0.357), respectively. The DBBM fragment group revealed similar bone thickness values as compared with the DBBM granules group, i.e., 0.26 mm (CI 0.23–0.29) versus 0.25 mm (CI 0.22–0.27, p = 0.641), respectively. The histological evaluation supported the micro-CT observations, displaying minor signs of porosity and resorption. The particle-size distribution analysis confirmed a shift towards smaller particle sizes in the DBBM fragment group. These findings suggest that DBBM fragments behave similarly to original DBBM granules in terms of bone morphological changes at augmented sites.


2017 ◽  
Vol 52 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Amy J. Naylor ◽  
Guillaume Desanti ◽  
Atif N. Saghir ◽  
Rowan S. Hardy

Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNFΔARE mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy ‘infliximab’ might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNFΔARE males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively. Analysis of breeding was examined retrospectively in TNFΔARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNFΔARE males receiving infliximab (control 6.6 arbitrary units [AU] ± 0.88 versus infliximab 4.4 AU ± 1.4; P < 0.05), while measures of pannus invasion and bone erosion by histology and micro-CT were markedly reduced. In the breeding groups, TNFΔARE males receiving infliximab injections sired more litters over their breeding lifespan (control 1.69 ± 0.22 versus infliximab 3.00 ± 0.19; P < 0.005). Furthermore, prior to infliximab, TNFΔARE males had a 26% risk of failing to sire any litters. This was reduced to 7% after the introduction of infliximab. This study is the first to report that regular administration of infliximab is effective at suppressing disease activity and improving animal welfare in TNFΔARE animals. In addition, we have shown that infliximab is highly efficacious in improving breeding behaviour and increasing the number of litters sired by TNFΔARE males.


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