scholarly journals The Small Molecule Components of Human Synovial Fluid and Bovine Calf Serum that Correlate with Cobalt Chrome (CoCrMo) Wear

Author(s):  
Matthew Jaggard ◽  
Harriet Stevenson ◽  
Claire Boulange ◽  
Goncalo Graca ◽  
Pouya Akhbari ◽  
...  

Abstract Background:Implant wear in joint replacements is influenced by the chemical and physical properties of human synovial fluid (HSF). In vitro testing for implant wear uses 25% weight bovine calf serum (25BCS) to substitute for HSF, due to similar rheology and total protein content. However, previous studies have shown differences in the macromolecular composition. We aimed to evaluate the differences in small molecule composition between fluids and correlate these differences with their effects on implant material wear.Methods:HSF was harvested from osteoarthritis patients undergoing primary knee replacement (n=14). Nuclear magnetic resonance (NMR) spectroscopy with linear regression modelling analysed the metabolites present in HSF and commercially sourced 25BCS and investigated the differences. Wear properties of the fluids were evaluated using a validated quantitative laboratory bench-test utilising a cobalt/chromium/molybdenum (CoCrMo) ball oscillating against a CoCrMo disc and analysing the resulting wear scar. The variation in metabolite levels in both HSF and 25BCS was correlated to the wear properties of the fluids.Results:Differences in the levels of metabolites, lipids, and glycosaminoglycans (GAG) were observed between HSF and 25BCS: significance was confirmed by O-PLS-DA (p<0.05). The wear of CoCrMo was found to strongly correlate with the macromolecules GAG and proteins that potentially bind to glucose and citrate. Conclusions:The small molecule concentration differences between the fluids questions the validity of 25BCS as a model for wear analysis. The demonstration of variable metabolites present in HSF which correlate with material wear has implications for implant failure and targeted therapeutic manipulation of these metabolites. Trial Registration:Ethical approval was granted by the NRES Committee London, Chelsea, UK on the 12th May 2015. The study was performed in accordance with the ethical standards in the 1964 Declaration of Helsinki.

1972 ◽  
Vol 126 (5) ◽  
pp. 1073-1080 ◽  
Author(s):  
Irwin Scher ◽  
David Hamerman

1. A compound of hyaluronate and protein, called hyaluronate–protein was isolated from pooled human synovial fluids by caesium chloride density-gradient ultracentrifugation. 2. The isolated hyaluronate–protein was labelled with [125I]iodide and the following studies were done. (a) Ultracentrifugation in caesium chloride showed that the protein moiety (125I counts) and hyaluronate (hexuronate) sedimented together in the middle of the gradient. (b) The labelled hyaluronate–protein was treated with trypsin, and ultracentrifugation showed that peptide fragments (125I counts) were dispersed throughout the gradient, indicating proteolytic digestion. Hyaluronate sedimented in the middle of the gradient. (c) The labelled hyaluronate–protein was digested with streptococcal hyaluronidase, and ultracentrifugation showed that hyaluronate fragments were dispersed throughout the gradient, indicating digestion of the polysaccharide. The protein moiety, without attached hyaluronate, now sedimented at the top of the gradient. (d) Ultracentrifugation of labelled hyaluronate–protein in 4m-guanidinium chloride showed that protein and hyaluronate sedimented together. 3. These studies confirm that hyaluronate is combined with a small quantity of protein in normal human synovial fluid. A mild method for the rapid isolation of hyaluronate–protein in good yield is described.


2017 ◽  
Vol 487 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Farong Ou ◽  
Kai Su ◽  
Jiadong Sun ◽  
Wenting Liao ◽  
Yu Yao ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
María Teresa Martín Monreal ◽  
Alexandra Stripp Rebak ◽  
Laura Massarenti ◽  
Santanu Mondal ◽  
Ladislav Šenolt ◽  
...  

Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, is involved in the breakage of self-tolerance in anti-CCP-positive rheumatoid arthritis. This reaction is catalyzed by peptidyl arginine deiminases (PADs), of which PAD2 and PAD4 are thought to play key pathogenic roles. Small-molecule PAD inhibitors such as the pan-PAD inhibitor BB-Cl-amidine, the PAD2-specific inhibitor AFM-30a, and the PAD4-specific inhibitor GSK199 hold therapeutic potential and are useful tools in studies of citrullination. Using an ELISA based on the citrullination of fibrinogen, we found that AFM-30a inhibited the catalytic activity of PADs derived from live PMNs or lysed PBMCs and PMNs and of PADs in cell-free synovial fluid samples from RA patients, while GSK199 had minor effects. In combination, AFM-30a and GSK199 inhibited total intracellular citrullination and citrullination of histone H3 in PBMCs, as determined by Western blotting. They were essentially nontoxic to CD4+ T cells, CD8+ T cells, B cells, NK cells, and monocytes at concentrations ranging from 1 to 20 μM, while BB-Cl-amidine was cytotoxic at concentrations above 1 μM, as assessed by flow cytometric viability staining and by measurement of lactate dehydrogenase released from dying cells. In conclusion, AFM-30a is an efficient inhibitor of PAD2 derived from PBMCs, PMNs, or synovial fluid. AFM-30a and GSK199 can be used in combination for inhibition of PAD activity associated with PBMCs but without the cytotoxic effect of BB-Cl-amidine. This suggests that AFM-30a and GSK199 may have fewer off-target effects than BB-Cl-amidine and therefore hold greater therapeutic potential.


2021 ◽  
Author(s):  
Ula von Mentzer ◽  
Tilia Selldén ◽  
LOISE Råberg ◽  
Gizem Erensoy ◽  
Anna-Karin Hultgård-Ekwall ◽  
...  

<div>Intra-articular drug delivery strategies aiming to deliver drugs in diseases affected by cartilage-related issues are using electrostatic interactions to penetrate the dense cartilage matrix. This enables delivery of sufficient drug concentrations to the chondrocytes to mediate the desired therapeutic effect. As it is well known that size and charge of nanoparticles affects its interactions with the surrounding biological fluids, where proteins adsorb to the NP surface, resulting in a protein corona. There are, however, no studies investigating how the formed protein coronas affect cartilage uptake and subsequent cellular uptake, nor how they affect other cells present in the synovium of such diseases. Here, we explore the differences between the protein coronas that form when NP are incubated in synovial fluid from osteoarthritic and rheumatoid arthritis patients and compare this to results obtained using fetal calf serum (FCS), as guide for researchers working on joint drug delivery. We demonstrate that the protein corona indeed affects the uptake into cartilage, where there are major differences between the model proteins in fetal calf serum, as compared to synovial fluid from rheumatoid arthritis patients as well as osteoarthritis patients. The data suggests that when developing drug delivery vehicles for joint diseases that leverages electrostatic interactions and size, the interactions with proteins in the biological milieu is highly relevant to consider.</div>


Author(s):  
H. Brouwers ◽  
J.H. von Hegedus ◽  
R.E.M. Toes ◽  
T.W.J. Huizinga ◽  
M.A. Giera ◽  
...  

2009 ◽  
Vol 34 (4) ◽  
pp. 101-108 ◽  
Author(s):  
Zhimin Cao ◽  
Clint West ◽  
Carol S. Norton-Wenzel ◽  
Robert Rej ◽  
Faith B. Davis ◽  
...  

Author(s):  
S Flanagan ◽  
E Jones ◽  
C Birkinshaw

New material combinations and designs of artificial hip implants are being introduced in an effort to improve proprioception and functional longevity. Larger joints in particular are being developed to improve joint stability, and it is thought that these larger implants will be more satisfactory for younger and more physically active patients. The study detailed here used a hip friction simulator to assess the friction and lubrication properties of large-diameter hip bearings of metal-on-metal and ceramic-on-reinforced-polymer couplings. Joints of different diameters were evaluated to determine what effect, if any, bearing diameter had on lubrication. In addition, the effects of lubricant type are considered, using carboxymethyl cellulose and bovine calf serum, and the physiological lubricant is shown to be considerably more effective at reducing friction. The frictional studies showed that the metal-on-metal joints worked under a mixed lubrication regime, producing similar friction factor values to each other. The addition of bovine calf serum (BCS) reduced the friction. The ceramic-on-reinforced-polymer samples were shown to operate with high friction factors and mixed lubrication. When tested with BCS, the larger-diameter bearings showed a decrease in friction compared with the smaller-size bearings, and the addition of BCS resulted in an increase in friction, unlike the metal-on-metal system. The study demonstrated that the component's diameter had little or no influence on the lubrication and friction of the large bearing combinations tested.


2016 ◽  
Vol 24 ◽  
pp. S166
Author(s):  
C. Galeano-Garces ◽  
S.M. Riester ◽  
E.T. Camilleri ◽  
H.S. Ryan ◽  
J. Smith ◽  
...  

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