scholarly journals Early subchondral bone changes in an osteoarthritis model in wild type and tgf-alpha knockout mice

2014 ◽  
Vol 22 ◽  
pp. S350
Author(s):  
H. Fang ◽  
I. Welch ◽  
D. Cai ◽  
F. Beier
2021 ◽  
Vol 11 (15) ◽  
pp. 7118
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen James Renaud ◽  
Christopher Thomas Appleton ◽  
...  

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 825.2-826
Author(s):  
M. Jansen ◽  
A. Ooms ◽  
T. D. Turmezei ◽  
J. W. Mackay ◽  
S. Mastbergen ◽  
...  

Background:In addition to cartilage degeneration, knee osteoarthritis (OA) causes bone changes, including cortical bone thickening, subchondral bone density decrease, and bone shape changes as a result of widening and flattening condyles and osteophyte formation. Knee joint distraction (KJD) is a joint-preserving treatment for younger (<65 years) knee OA patients that has been shown to reverse OA cartilage degradation. On radiographs, KJD showed a decrease in subchondral bone density and an increase in osteophyte formation. However, these bone changes have never been evaluated with a 3D imaging technique.Objectives:To evaluate cortical bone thickness, subchondral trabecular bone density, and bone shape on CT scans before and one year after KJD treatment.Methods:19 KJD patients were included in an extended imaging protocol, undergoing a CT scan before and one year after treatment. Stradview v6.0 was used for semi-automatic tibia and femur segmentation from axial thin-slice (0.45mm) CT scans. Cortical bone thickness (mm) and trabecular bone density (Hounsfield units, HU) were measured with an automated algorithm. Osteophytes were excluded. Afterwards, wxRegSurf v18 was used for surface registration. Registration data was used for bone shape measurements. MATLAB R2020a and the SurfStat MATLAB package were used for data analysis and visualization. Two-tailed F-tests were used to calculate changes over time. Two separate linear regression models were used to show the influence of baseline Kellgren-Lawrence grade and sex on the changes over time. Statistical significance was calculated with statistical parametric mapping; a p-value <0.05 was considered statistically significant. Bone shape changes were explored visually using vertex by vertex displacements between baseline and follow-up. Patients were separated into two groups based on whether their most affected compartment (MAC) was medial or lateral. Only patients with axial CT scans at both time points available for analysis were included for evaluation.Results:3 Patients did not have complete CTs and in 1 patient the imaged femur was too short, leaving 16 patients for tibial analyses and 15 patients for femoral analyses. The MAC was predominantly the medial side (medial MAC n=14; lateral n=2). Before treatment, the MAC cortical bone was compared to the rest of the joint (Figure 1). One year after treatment, MAC cortical thickness decreased, although this decrease of up to approximately 0.25 mm was not statistically significant. The trabecular bone density was also higher before treatment in the MAC, and a decrease was seen throughout the entire joint, although statistically significant only for small areas on mostly the MAC where this decrease was up to approximately 80 HU (Figure 1). Female patients and patients with a higher Kellgren-Lawrence grade showed a somewhat larger decrease in cortical bone thickness. Trabecular density decreased less for patients with a higher Kellgren-Lawrence grade, and female patients showed a higher density decrease interiorly while male patients showed a higher decrease exteriorly. None of this was statistically significant. The central areas of both compartments showed an outward shape change, while the outer ring showed inward changes.Conclusion:MAC cortical bone thickness shows a partial decrease after KJD. Trabecular bone density decreased on both sides of the joint, likely as a direct result of the bicompartmental unloading. For both subchondral bone parameters, MAC values became more similar to the LAC, indicating (partial) subchondral bone normalization in the most affected parts of the joint. The bone shape changes may indicate a reversal of typical OA changes, although the inward difference that was seen on the outer edges may be a result of osteophyte-related changes that might have affected the bone segmentation. In conclusion, KJD treatment shows subchondral bone normalization in the first year after treatment, and longer follow-up might show whether these changes are a temporary result of joint unloading or indicate more prolonged bone changes.Disclosure of Interests:None declared.


Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 101042
Author(s):  
Gundula Rösch ◽  
Dominique Muschter ◽  
Karima El Bagdadi ◽  
Shahed Taheri ◽  
Andrea Meurer ◽  
...  

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.


Author(s):  
Naoki Ishii ◽  
Takujiro Homma ◽  
Jaeyong Lee ◽  
Hikaru Mitsuhashi ◽  
Ken-ichi Yamada ◽  
...  

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.


2013 ◽  
Vol 10 (1) ◽  
Author(s):  
Sachiko Tanaka ◽  
Atsuko Ishii ◽  
Hirokazu Ohtaki ◽  
Seiji Shioda ◽  
Takemi Yoshida ◽  
...  

2013 ◽  
Vol 111 (6) ◽  
pp. 979-986 ◽  
Author(s):  
Gabriel G. Dorighello ◽  
Juliana C. Rovani ◽  
Christopher J. F. Luhman ◽  
Bruno A. Paim ◽  
Helena F. Raposo ◽  
...  

Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.


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