scholarly journals The complexity of molecular processes in osteoarthritis of the knee joint

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 366-375
Author(s):  
Paweł Łęgosz ◽  
Sylwia Sarzyńska ◽  
Łukasz Pulik ◽  
Daniel Kotrych ◽  
Paweł Małdyk

AbstractOsteoarthritis (OA) is a common medical problem leading to chronic pain and physical disability among the world’s population. Analyzing the molecular background of the degenerative arthritis creates the potential for developing novel targeted methods of treatment. Fifty samples of meniscus, anterior cruciate ligaments (ACLs) and articular surfaces were collected from patients who underwent total knee arthroplasty in 2016. Enzyme-linked immunosorbent assay was used to assess the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), transforming growth factor-β1 and LUMINEX for MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. The collected data were correlated with the severity of radiological OA, demographic data and clinical scales. Strong positive correlations in the concentration of metalloproteinases and proinflammatory cytokines, TNF-α (MMP-2 and MMP-13) and IL-6 (MMP-13), were identified. MMP-13 had a positive correlation with the concentration of MMP-1, MMP-2 and MMP-9. Negative correlation coefficient exists between clinical conditions measured with the Western Ontario and McMaster Universities Osteoarthritis Index scale and the level of TNF-α and MMP-1. The TNF-α concentration was lower in the cartilage of the articular surface among patients who took non-steroidal anti-inflammatory drugs periodically. The decrease in MMP-2 in the cartilage of the articular surface corresponded with the severity of radiological OA on the Kellgren–Lawrence scale. Current treatment methods for OA do not stop disease progression. Identifying signaling pathways and molecular particles engaged in OA and their correlations with the patient’s clinical condition brings new therapeutic possibilities.

1998 ◽  
Vol 275 (4) ◽  
pp. L637-L644 ◽  
Author(s):  
Yu-Chen Lee ◽  
D. Eugene Rannels

Type II pulmonary epithelial cells respond to anthracite coal dust PSOC 867 with increased synthesis of extracellular matrix (ECM) components. Alveolar macrophages modulate this response by pathways that may involve soluble mediators, including tumor necrosis factor-α (TNF-α) or transforming growth factor-β1 (TGF-β1). The effects of TNF-α (10 ng/ml) and/or TGF-β1 (2 ng/ml) were thus investigated in dust-exposed primary type II cell cultures. In control day 1 or day 3 cultures, TNF-α and/or TGF-β1 had little or no effect on the synthesis of type II cellular proteins, independent of whether the cells were exposed to dust. With PSOC 867 exposure, where ECM protein synthesis is elevated, TNF-α and TGF-β1 further increased both the absolute and relative rates of ECM synthesis on day 3 but had little effect on day 1. Each mediator increased expression of fibronectin mRNA, as well as of ECM fibronectin content, in a manner qualitatively similar to their effects on synthesis. Thus TNF-α and TGF-β1 modulate both ECM synthesis and fibronectin content in coal dust-exposed type II cell cultures.


2016 ◽  
Vol 45 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Matthias Kieb ◽  
Frank Sander ◽  
Cornelia Prinz ◽  
Stefanie Adam ◽  
Anett Mau-Möller ◽  
...  

Background: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. Purpose: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. Study Design: Controlled laboratory study. Methods: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance). Results: All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL). Conclusion: Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients. Clinical Relevance: The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared.


Planta Medica ◽  
2020 ◽  
Vol 86 (06) ◽  
pp. 405-414 ◽  
Author(s):  
Yasamin Roohbakhsh ◽  
Vafa Baradaran Rahimi ◽  
Samaneh Silakhori ◽  
Hamed Rajabi ◽  
Pouria Rahmanian-Devin ◽  
...  

AbstractPostoperative adhesions are regarded as the major complication following abdominal surgery. Rosmarinus officinalis has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of R. officinalis against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v R. officinalis treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1β, and TNF-α), growth factors (transforming growth factor-β1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1β, TNF-α, transforming growth factor-β1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. R. officinalis treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that R. officinalis markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, R. officinalis may be a potential candidate for the management of postoperative peritoneal adhesion.


2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Vinícius da Cunha Lisboa ◽  
Marcelo Ribeiro-Alves ◽  
Raquel da Silva Corrêa ◽  
Isabelle Ramos Lopes ◽  
Thiago Thomaz Mafort ◽  
...  

ABSTRACT Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically confirmed or not) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB) (n = 25) patients. The levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, IFN-γ, tumor necrosis factor (TNF), IP-10, transforming growth factor β1 (TGF-β), and ADA were determined using cytometric bead assay, enzyme-linked immunosorbent assay (ELISA), or biochemical tests. IFN-γ, IP-10, TNF, TGF-β, and ADA quantified in PF showed significantly higher concentrations in PlTB patients than in nTB patients. When blood and PF were compared, significantly higher concentrations of IL-6 and IL-10 in PF were identified in both groups. TGF-β, solely, showed significantly increased levels in PF and blood from PlTB patients when both clinical specimens were compared to those from nTB patients. Principal-component analysis (PCA) revealed a T helper type 1 (Th1) pattern attributed mainly to higher levels of IP-10, IFN-γ, TGF-β, and TNF in the pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases, rather than other causes of exudative effusion commonly considered in the differential diagnosis of PlTB.


2000 ◽  
Vol 68 (3) ◽  
pp. 1465-1473 ◽  
Author(s):  
Beinan Wang ◽  
Ellen Kraig ◽  
David Kolodrubetz

ABSTRACT Campylobacter rectus is a periodontal pathogen with a 150-kDa protein on its cell surface. This protein forms a paracrystalline lattice, called the S-layer, surrounding the outer membrane of this gram-negative bacterium. To initiate a genetic analysis of the possible role of the S-layer in the initial interaction of C. rectus with host epithelial cells, C. rectus strains lacking the S-layer protein gene (crsA) were constructed by allelic exchange mutagenesis. Surprisingly, the lack of the S-layer had only a minor effect on the interaction of C. rectus with HEp-2 epithelial cells; CrsA+ cells were 30 to 50% more adherent than were CrsA− bacteria. Since the host cell expression of cytokines appears to play an important role in the pathogenesis of periodontal diseases, the effect of the S-layer on the epithelial cell cytokine response was also examined by quantitative reverse transcriptase PCR and enzyme-linked immunosorbent assay. Although there were no changes in the mRNA levels for the anti-inflammatory cytokines interleukin-1 receptor agonist (IL-1ra), IL-13, and transforming growth factor β, the expression and secretion of the proinflammatory cytokines IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) were significantly induced by both wild-type C. rectus and CrsA− bacteria. Interestingly, the kinetics of cytokine induction differed for the CrsA+ and CrsA−bacteria. At early time points, the HEp-2 cells challenged with CrsA− bacteria produced higher levels of IL-6, IL-8, and TNF-α mRNA and protein than did cells challenged with CrsA+ bacteria. We conclude that C. rectus may help initiate periodontitis by increasing the expression of proinflammatory cytokines and that the S-layer may temper this response to facilitate the survival of C. rectus at the site of infection.


1999 ◽  
Vol 67 (9) ◽  
pp. 4977-4981 ◽  
Author(s):  
Douglas J. Perkins ◽  
Peter G. Kremsner ◽  
Daniela Schmid ◽  
Mary A. Misukonis ◽  
Meghan A. Kelly ◽  
...  

ABSTRACT Plasmodium falciparum malaria is an important cause of morbidity and mortality in children. Factors that determine the development of mild versus severe malaria are not fully understood. Since host-derived nitric oxide (NO) has antiplasmodial properties, we measured NO production and NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMC) from healthy Gabonese children with a history of prior mild malaria (PMM) or prior severe malaria (PSM) caused by P. falciparum. The PMM group had significantly higher levels of NOS activity in freshly isolated PBMC and higher NO production and NOS activity in cultured PBMC. The investigation of NO-modulating cytokines (e.g., interleukin 12, gamma interferon, tumor necrosis factor alpha [TNF-α], and transforming growth factor β1) as an explanation for differing levels of NOS activity revealed that plasma levels of TNF-α were significantly higher in the PSM group. Our results suggest that NOS/ NO and TNF-α are markers for prior disease severity and important determinants of resistance to malaria.


2019 ◽  
Vol 31 (6) ◽  
pp. 1049 ◽  
Author(s):  
Vahid Ehsani ◽  
Maryam Mortazavi ◽  
Khodayar Ghorban ◽  
Maryam Dadmanesh ◽  
Reza Bahramabadi ◽  
...  

Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-β were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-β and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-β production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.


2017 ◽  
Vol 313 (2) ◽  
pp. F414-F422 ◽  
Author(s):  
Salma Malik ◽  
Kapil Suchal ◽  
Sana Irfan Khan ◽  
Jagriti Bhatia ◽  
Kamal Kishore ◽  
...  

Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5–20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose >250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-β1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-α, IL-6, and NF-κB expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.


2014 ◽  
Vol 17 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Melissa M. Shelton ◽  
Donna L. Schminkey ◽  
Maureen W. Groer

A secondary pilot study was carried out as part of a larger parent study of thyroid function in pregnancy and postpartum. All women in the parent study ( N = 631) had blood samples, demographic data, and measures of perceived stress and dysphoric moods collected between 16 and 26 weeks’ gestation. The current study was completed with a subset of 105 pregnant women to examine the relationships among perceived stress, depression, plasma cortisol, and cytokines during the second trimester of pregnancy. Stress was measured using Cohen’s Perceived Stress Scale and dysphoric moods using the Profile of Mood States Depression/Dejection Scale. Cytokines were measured by a 12-plex analysis on a Luminex-200, and cortisol was measured by enzyme-linked immunosorbent assay on stored plasma samples. Stress and depression scores were highly correlated, and depressive symptoms were inversely correlated with 3 of the 12 cytokines: interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-7. Cortisol was inversely correlated with proinflammatory cytokines (IL-1β and TNF-α) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). These data support the new conceptualizations of normal pregnancy as an inflammatory state that is carefully regulated, as both excessive and inadequate inflammation are potentially hazardous to the health of the pregnancy and fetus.


2019 ◽  
Vol 10 (3) ◽  
pp. 245-252 ◽  
Author(s):  
P.D. Kusumo ◽  
B. Bela ◽  
H. Wibowo ◽  
Z. Munasir ◽  
I.S. Surono

The immature intestinal immune system in young children develops as it comes into contact with dietary and microbial antigens in the gut. Intestinal microbiota plays a significant role in host defence mechanisms as shown by inflammatory responses towards potential pathogens. We investigated the probiotic function of Lactobacillus plantarum IS-10506 of ‘dadih’ origin in modulating immune response in young children. We aimed to assess its effect on their immune response by assessing transforming growth factor-β1 (TGF-β1) and tumour necrosis factor-α (TNF-α) responses and faecal secretory immunoglobulin A (sIgA) titre in a randomised, double-blinded placebo-controlled trial in 12-24-month-old children (n=38). We used four treatment groups for a 90-day supplementation period: placebo (n=11), probiotic (n=9), zinc (n=8) and probiotic and zinc (n=10). Faecal sIgA, plasma TGF-β1 and TNF-α titre were evaluated using the enzyme-linked immunosorbent assay standard technique. Statistical analysis divided the results (pre/post treatment) into high (>1) and low (<1) ratios. The results showed that faecal sIgA titre increased in all treatment groups compared with the control (placebo) and significantly increased in the probiotic group (P=0.05). In addition, the TGF-β1 ratio in the zinc group was significantly higher (P=0.05) than that in the placebo group. We observed a significant positive correlation between TGF-β1/TNF-α and faecal sIgA (r=0.27, P=0.04). Post hoc test results revealed that zinc supplementation has a significant effect on body-weight gain. Taken together, probiotic L. plantarum IS-10506 supplementation stimulates TGF-β1, which in turn increases the production of sIgA, in line with the significant correlation between TGF-β1/TNF-α and faecal sIgA.


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