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It has traditionally been believed that only the human collagenases (matrix metalloproteinase-1, -8, and -13) are capable of initiating the degradation of collagens. Here, we show that human trypsin-2 is also capable of cleaving the triple helix of human cartilage collagen type II. We purified human trypsin-2 and tumor-associated trypsin inhibitor by affinity chromatography whereas collagen type II was purified from cartilage extracts using pepsin digestion and salt precipitation. Degradation of type II collagen and gelatin by trypsin-2 was demonstrated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, zymography, and mass spectrometry, and tumor-associated trypsin inhibitor specifically inhibited this degradation. Although human trypsin-2 efficiently digested type II collagen, bovine trypsin did not. Furthermore, immunohistochemical staining detected trypsin-2 in the fibroblast-like synovial lining and in stromal cells of human rheumatoid arthritis synovial membrane. These findings were confirmed by reverse transcriptase-polymerase chain reaction and nucleotide sequencing. Trypsin-2 alone and complexed with alpha(1)-proteinase inhibitor were also detected in the synovial fluid of affected joints by time-resolved immunofluorometric assay, suggesting that trypsin-2 is activated locally. These results are the first to assess the ability of human trypsin to cleave human type II collagen. Thus, trypsin-2 and its regulators should be further studied for use as markers of prognosis and disease activity in rheumatoid arthritis.

Osteoarthritis(OA) is a very common wear-and tear arthritis occurring in the knee joints. It is caused due to many factors like excess body weight, age etc., which leads to the drying of synovial fluid. The synovial fluid is a mixture of hyaluronic acid as a main constituent and body proteins which gives a cushioning effect for the joint in order to prevent the bones from rubbing against each other which causes friction in between. The study of wear, friction and lubrication is called tribology. This study when integrated with biological systems is known as bio tribology. This study helps us in understanding the mechanisms occurring in the joints. There are many treatments to cure Osteoarthritis(OA) like Total Knee Replacements, Hyaluronic Acid injections and many other pharmacological and non-pharmacological methods. The present paper reviews about articles which have internal relation with tribology, biomechanics, boundary lubrication, biomaterials and modelling of human knee joint using finite element analysis. The ultimate objective of the present review is to confer the total information about the tribological aspects which are related to the knee joints. So that this paper would be useful for the researchers to work on biocompatible fluids and their analyses which may give solution for the Osteoarthritis(OA)

A mathematical model of lubrication of human synovial joints under squeeze-film conditions is presented in this several-part paper. Squeeze-film action leads to a concentration of hyaluronic-acid-protein macromolecular complex in the synovial fluid between the approaching cartilage surfaces as a result of the diffusion of water and low molecular weight substances through the cartilage surfaces or along the gap. Increasing viscosity of synovial fluid delays the approach of these surfaces and the formation of stable gels then protects cartilage, if sliding motion ensues, before fluid film lubrication is restored. In Part I of the present paper synovial fluid is considered as a mixture of two incompressible fluids. The material parameters of this mixture of fluids are found using previously published experimental results. Squeeze-film analysis is carried out for the axially symmetric synovial film.

This paper presents a mini-review of investigations performed by the authors in the field of hydrodynamic theory of lubrication of biological systems and synthetic processing of results to indicate the influence of biologically live material properties on biological liquid viscosity variations. The goal of the presented study was to demonstrate a new principle of a general mathematical theory applied to the mechanism of hydrodynamic lubrication of human joint cartilage surfaces with phospholipids bilayer and to indicate analytical solutions of hydrodynamic pressure, temperature and bio-fluid velocity components. Moreover, 3D variations of dynamic synovial fluid viscosity are assessed, particularly its variations across the entire film thickness. A new 3D analytical and numerical model has been elaborated on the basis of tribology methods, based on the assumptions of an ultra-thin boundary layer of non-Newtonian fluid. The analysed elements also included phospholipid concentrations, power hydrogen ion and collagen fiber concentrations in synovial, biological fluids, as well as electrostatic field, cartilage or biological surface wettability. The obtained results of our analysis demonstrate relationships which occur among hydrodynamic pressure, human joint load carrying capacity and phospholipid bilayer in the cartilage superficial layer. According to the best knowledge of the Authors, the obtained results may find applications in a broad scope of spatiotemporal models in biology and health science.

Rheumatoid arthritis (RA) is a common autoimmune disease that mainly affects the joints. It is characterized by synovial inflammation, which may result in cartilage and bone destruction. The present paper develops a mathematical model of chronic RA. The model is represented by a system of partial differential equations (PDEs) in the synovial fluid, the synovial membrane, and the cartilage. The model characterizes the progression of the disease in terms of the degradation of the cartilage. More precisely, we assume a simplified geometry in which the synovial membrane and the cartilage are planar layers adjacent to each other. We then quantify the state of the disease by how much the cartilage layer has decreased, or, equivalently, how much the synovial layer has increased. The model is used to evaluate treatments of RA by currently used drugs, as well as by experimental drugs.

Importance Biomarkers have promising potential to provide a cost-effective tool to identify patients with femoroacetabular impingement (FAI) who are most at risk and who may benefit most from early joint preservation surgery. Objective To assess the potential role of biomarkers in the diagnosis and prognosis of FAI. Evidence review Three databases (PubMed, Ovid (MEDLINE) and Embase) were searched on 20 August 2017 from database inception, and two reviewers independently and in duplicate screened the resulting literature. Methodological quality of all included papers was assessed using the Methodological Index for Non-Randomized Studies criteria. The results are presented in a narrative summary fashion using descriptive statistics including means, proportions and ranges. Findings Seven studies (one retrospective laboratory series and six controlled laboratory studies) were identified including a total of 227 patients. The mean age of the patients was 41.6 years (range: 13–80), with a mean follow-up period of 29.9 months (SD=3.2). Markers of articular cartilage breakdown, including cartilage oligomeric matrix protein (COMP) and fibronectin–aggrecan complex (FAC), were identified in high concentrations in the serum and synovial fluid of patients with FAI, respectively. Moreover, mRNA expression of catabolic cytokines in the articular cartilage of patients with FAI has been reported. Conclusions and relevance Although not yet used in clinical settings, several biomarkers of articular cartilage damage have been identified in the serum, synovial fluid and articular cartilage of patients with FAI. These findings provide promising insight into the potential role of biomarkers in guiding clinical practice and assisting with patient selection and preoperative counselling in patients with FAI and should be evaluated further. Level of evidence IV, systematic review of level III and IV studies.

Osteoarthritis (OA) is a degenerative disease leading to the breakdown of the hyaline cartilage between a varieties of diarthrodial joints such as the knee joint, carpals of the wrist and etc. When the cartilage is affected by trauma or wear and tear, Osteolysis may occur; broken debris of cartilage found within the synovial fluid may be recognised as a pathogen and therefore, the body’s autoimmune response will directly target the cartilage for destruction. Cytokines are proteins/peptides of glycoproteins that are secreted by cells and are involved in interaction and communication between cells. Transforming Growth Factors Beta 1 (TGF-β1) is one of well-known cytokines and had shown many effects on cellular biology including simulation or inhibition of cell proliferation, differentiation, production of extracellular matrix (ECM), remodelling, and producing both hormones and growth factors. On the other hand, Photonics recently play an important role for treatment of OA. The main aim of this review article is to investigate the effect of TGF-β1 in treatment of OA. Other important aim of this work is to explore the broad applications of optics and photonics in biomedical applications including treatment of OA. Biomedical applications of photonics have broad aspects including laser, carbon nanotubes (CNTs), quantum dots (QDs) and graphene and photodynamic therapy (PDT) which discussed in this review paper.

The present paper explores the effect of synovial fluid composition on lubricant film formation in hip replacements. The measurements were realized utilizing pendulum hip joint simulator, while the film thickness was evaluated using optical interferometry. Contact couples consisted of metal and ceramic femoral heads articulating with glass acetabular cups. As the test lubricants, various model fluids were employed. Initially, static tests, aimed on the effect of material and load on adsorption, were conducted. It was found that adsorbed film thickness increases independently of the head material. Consequently, swinging flexion-extension experiments were realized, revealing that the film formation is substantially affected by composition of model fluid. The thickest film was observed when higher concentration of hyaluronic acid and phospholipids was applied.

In this paper, we have worked for the impact of induced magnetic field on peristaltic motion of a non-Newtonian, incompressible, synovial fluid in an asymmetric channel. We have solved the problem for two models, Model-1 which behaves as shear thinning fluid and Model-2 which behaves as shear thickening fluid. The problem is solved by using modified Adomian Decomposition method. It has seen that two models behave quite opposite to each other for some parameters. The impact of various parameters on u , dp dx , Δ p and induced magnetic field b x have been studied graphically. The significant findings of this study is that the size of the trapped bolus and the pressure gradient increases by increasing M for both models.

The present paper explores the effect of viscosupplementation on the friction of articular cartilage depending on the rheology of viscosupplements. The experiments were realized on rotational rheometers and a tribometer in pin-on-plate configuration. Five commercially available viscosupplements and their mixtures with synovial fluid were tested. The results showed differences by the order of magnitudes between viscosupplements viscosity and no viscoelastic properties in some of them. The friction was substantially affected by the addition of viscosupplement into the model synovial fluid. In most cases, mixtures of synovial fluid and viscosupplement even showed similar friction as clear viscosupplements. This study is the basis for a better understanding of the short-term changes in articular cartilage frictional behavior after the viscosupplementation of synovial joint.

Summary Objective Solutes and interstitial water are naturally transported from cartilage by load-induced interstitial fluid pressures. Fluid and solute recovery during joint articulation have been primarily attributed to passive diffusion and mechanical ‘pumping' from dynamic loading. This paper tests if the sliding action of articulation is a significant and independent driver of fluid and solute transport in cartilage. Design The large osteochondral samples utilized in the present study preserve the convergent wedges necessary for physiological hydrodynamics. Following static load-induced fluid exudation and prior to sliding, a fluorescent solute (AlexaFluor 633) was added to the lubricant bath. In situ confocal microscopy was used to quantify the transport of solute from the bath into the buried stationary contact area (SCA) during sliding. Results Following static exudation, significant reductions in friction and strain during sliding at 60 mm/s were accompanied by significant solute transport into the inaccessible center of the buried contact; no such transport was detected for the 0- or 1 mm/s sliding conditions. The results suggest that external hydrodynamic pressures from sliding induced advective flows that carried solutes from the bath toward the center of contact. Conclusions These results provide the first direct evidence that the action of sliding is a significant contributor to fluid and solute recovery by cartilage. Furthermore, they indicate that the sliding-induced transport of solutes into the buried interface was orders of magnitude greater than that attributable to diffusion alone, a result with critical implications for disease prevention and tissue engineering.

Aims To explore the therapeutic effect of miR-129-5p carried by exosomes from Human Synovial Mesenchymal Stem Cell (HS-MSC) on osteoarthritis(OA). Materials and methods The levels of miR-129-5p and high mobility group protein -1 (HMGB1) and interleukin-1β (IL-1β) in the joint fluid of OA patients were respectively detected via real-time quantitative reverse transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-1β was taken to act on chondrocytes for the establishment of OA model in vitro. Ultracentrifugation was conducted to isolate HS-MSC exosomes (HS-MSC-Exo) from the supernatant. Western blot and ELISA were carried out to measure the expression of iNOS, COX2, MMP13, Collagen 2, TLR4, NF-κB, Caspase3, Bcl-2, HMGB1 in chondrocytes. Flow cytometry was conducted to detect the apoptosis of chondrocytes. Besides, bioinformatics was employed to predict the targeted relationship between miR-129-5p and HMGB1, which was further verified via dual luciferase activity experiments. Key findings The results illustrated that miR-129-5p was decreased in OA patients and IL-1β-induced chondrocytes, while HMGB1 was notably upregulated. HS-MSC-Exo rich in miR-129-5p remarkably declined the inflammatory response and apoptosis of chondrocytes, while HS-MSC-Exo deficient in miR-129-5p increased the IL-1β-mediated inflammatory response and apoptosis of chondrocytes. In terms of mechanism, miR-129-5p targets the 3’UTR end of HMGB1 and inhibits IL-1β-mediated upregulation of HMGB1. Significance In a word, this paper proved that miR-129-5p, existing in HS-MSC-Exo, can suppress the IL-1β-mediated OA by inhibiting HMGB1 release.

Movement of the knee joint requires an effective lubrication mechanism. Synovial fluid is reported to serve this function. Synovial fluid is an extra cellular biofluid present in the synovial joint of living beings. Numerous studies have been conducted on the characteristics of synovial fluid. Total Knee Replacement is seen as a permanent cure to acute arthritic condition. Synovial fluid supplementation is seen to enhance the life of Total Knee Replacement Joints. Development of an effective synovial fluid for this purpose is being researched worldwide. This paper reviews the properties of synovial fluid as reported under various studies and can form the basis for development of a good artificial synovial fluid.

Using the apparatus and technique described in an earlier paper, (Kempson et al. 1971), indentation tests were performed on areas of cartilage of 0·125 in dia., in situ on, and distributed evenly over, the cartilage surface of the human femoral head. Curves of indentation vs. time were plotted for a physiological stress of approximately 400 lbf/in2. (28·2 kgf/cm2, 2·36 MN/m2). The stiffness of each area of cartilage was calculated from the appropriate indentation value, in the form of a creep modulus at 2 sec, using the equations described in the previous paper (see Appendix). Layered maps and histograms showing the variation of both cartilage stiffness and indentation are presented.

Summary Objective To review the literature on modulation of chondrocyte activities in the osteoarthritic joint, and to discuss these changes in relation to established hard and soft tissue repair paradigms, with an emphasis on transforming growth factor beta (TGFβ1)-mediated signaling which can promote either a chondrogenic or fibrogenic phenotype. Methods Papers addressing the close relationship between repair in general, and the specific post-injury response of joint tissues are summarized. Different interpretations of the role of TGFβ1 in the emergence of an "osteoarthritic" chondrocyte are compared and the phenotypic plasticity of "reparative" progenitor cells is examined. Lastly, emerging data on a central role for A-Disintegrin-And-Metalloproteinase-with-Thrombospondin-like-Sequences-5 (ADAMTS5) activity in modulating TGFβ1 signaling through activin receptor-like kinase 1 (ALK1) and activin receptor-like kinase 5 (ALK5) pathways is discussed. Results The review illustrates how a transition from ALK5-mediated fibrogenic signaling to ALK1-mediated chondrogenic signaling in joint cells represents the critical transition from a non-reparative to a reparative cell phenotype. Data from cell and in vivo studies illustrates the mechanism by which ablation of ADAMTS5 activity allows the transition to reparative chondrogenesis. Multiple large gene expression studies of normal and osteoarthritis (OA) human cartilages (CAs) also support an important role for TGFβ1-mediated pro-fibrogenic activities during disease progression. Conclusions We conclude that progressive articular CA damage in post-injury OA results primarily from biomechanical, cell biologic and mediator changes that promote a fibroblastic phenotype in joint cells. Since ADAMTS5 and TGFβ1 appear to control this process, agents which interfere with their activities may not only enhance endogenous CA repair in vivo , but also improve the properties of tissue-engineered CA for implantation.

In this short paper we study the linearized stability of the flow of a chemically reacting fluid in a cylindrical pipe, under the assumption that the length of the pipe is far greater than its diameter. The fluid models that are considered have relevance to the flow of both polymeric liquids that are capable of undergoing chemical reactions and biological fluids such as the synovial fluid whose viscosity changes due to the concentration of the hyaluronan. The viscosity of the class of fluids that we consider can increase or decrease due to the concentration of the chemical that is being carried by the fluid and it can also shear thin or shear thicken. We non-dimensionalize the equations governing the motion of the fluid and then carry out an approximation wherein we retain terms that are of order unity in the Reynolds number and Peclet number. We further simplify the problem by seeking a special semi-inverse solution, in the same spirit as that which is used in the study of classical Hagen-Poiseuille flow, and look for solutions for the velocity field and the concentration that vary only with the radial coordinate. Under the above mentioned approximation, one can obtain an exact solution for the basic flow which then allows us to analytically consider the stability of the base flow to sufficiently small disturbances. On the basis of earlier studies of such fluids in the modeling of biological fluids, especially the synovial fluid, we consider two types of variation of the viscosity with the concentration. We find that flows in the cylindrical pipe, within the context of our approximation, are stable to sufficiently small disturbances, for both variations of the viscosity that are considered.

In this paper, an alternative model for the synovial fluid in the human knee is proposed. The synovial fluid is modeled as a micromorphic fluid containing deformable material particles with 12 degrees of freedom, namely three translations, three rotations and six stretches and shears. Two micromorphic viscosity coefficients are introduced as functions of hyaluronan and PRG4/lubricin concentrations and are reconstructed by a genetic algorithm based on experimental data. The model is validated by applying it to well established rheological measurements of synovial fluid, such as shear-thinning ( Cooke et al., 1978 ).

Numerous methods have been proposed in the last 60 years for the determination of the time since death by chemical means. Many of them were reviewed by Schleyer in his monograph on the determination of the time since death by means of thanatochemistry about 40 years ago and none of these early methods has gained any practical value since they do not meet the demands in practice (being precise, reliable, giving an immediate result). While the earlier studies were mainly carried out on blood and cerebrospinal fluid (CSF) since the late 60s most investigations have been performed on vitreous humor (VH). This is mainly due to the fact that vitreous humor is topographically isolated and well protected, and thus, autolytic changes proceed slower compared to blood and CSF. The most studied parameter in VH is potassium and even nowadays reports on the postmortem rise of vitreous potassium are published, proposing new analytical methods or statistical evaluations. Chemical parameters studied for the determination of the time since death have to be differentiated according to the underlying process (catabolism, metabolic processes, pure autolysis and diffusion, putrefactive changes). In the present paper, recent studies on thanatochemistry are discussed regarding the underlying process, the analytical methods (for instance H magnetic resonance spectroscopy (1H MR spectroscopy), immunohistochemistry), the studied fluid compartment, the statistical evaluation and the precision of death time estimation. The value of chemical methods for the determination of the time since death is up to now very limited. This is supported by the fact that field studies on the reliability and precision of death time estimation by chemical means are still scarce in the literature.

Various molecular and inflammatory mediators, and matrix metabolites have been reported in the synovial fluid of patients with temporomandibular joint disorders. Additionally oxidative stress and the accumulation of free radicals may lead to tissue damage in all tissues, including the temporomandibular joint. These molecular events can trigger the degradation of collagen, hyaluronic acid, and proteoglycans, leading to the development of articular pathology. In this paper, the literature is reveiwed with an emphasis on synovial fluid, and the scientific evidence categorised to theoretically consider the aetiology and pathology of temporomandiblar joint disorders.

Articular cartilage is an extremely complex material; it exhibits unique properties, unmatched by man-made materials. It is widely thought that articular cartilage plays a major role in controlling both the lubrication and, more importantly, wear of synovial joints. Degenerative joint diseases, such as osteoarthritis, are thought to be related to the wear of articular cartilage. As the wear rate accelerates, the cartilage is completely worn away, leading to direct bone-to-bone contact, eventually requiring joint replacement surgery. Intensive research has been focused on the lubrication properties of synovial joints, while their wear characteristics and mechanisms still remain poorly researched. In this paper, preliminary results obtained from wear studies conducted on articular cartilage samples are described and discussed. Sheep knee joints were worn in a joint simulator for different periods of time. Two criteria, i.e. changes in surface morphology and in wear particle morphology, were used in wear assessment. The worn joints were compared to control (unworn) joints to determine the changes occurring. The surface morphology of articular cartilage was imaged using both scanning electron microscopy (SEM) and environmental SEM, with surface damage found to increase as the duration of wear tests increased. Environmental scanning electron microscopy (ESEM) has allowed the true surface of articular cartilage to be imaged in its natural state, without the need for fixation. ESEM imaging has revealed a surface layer that lies on top of the collagen matrix. The function of this surface layer is found to be disrupted by wear. Wear particles were also collected and characterised using numerical descriptors. The wear particles were observed to change shape and size as wear progresses.

A mixture model of synovial fluid filtration by cartilage in the human ankle joint during walking is presented for steady sliding motion of the articular surfaces. In the paper the cartilage surface zone is assumed worn out. The same model has been recently applied to the squeeze-film problem for the human hip joint loaded by the body weight during standing (Hlavácek, Journal of Biomechanics 26, 1145-1150, 1151-1160, 1993; Hlavácek and Novák, Journal of Biomechanics 28, 1193-1198, 1199-1205, 1995). The linear biphasic model for cartilage (elastic porous matrix + ideal fluid) due to Prof. V. C. Mow and his co-workers and the biphasic model for synovial fluid (viscous fluid + ideal fluid), as used in the above-mentioned squeeze-film problem, are applied. For the physiologic parameters of the ankle joint during walking, a continuous synovial fluid film about 1 microm thick is maintained under steady entraining motion according to the classical model without the fluid transport across the articular surface. This is not the case in the filtration model with the cartilage surface zones worn out. On the contrary, this filtration model indicates that synovial fluid is intensively filtrated by such cartilage, so that no continuous fluid film is maintained and a synovial gel layer, about 10(-8) m thick, develops over the majority of the contact. Thus, if the cartilage surface zones are worn out, boundary lubrication should prevail in the ankle joint under steady sliding motion for the mean values of loading and the sliding velocity encountered in walking cycle.

A mixture model of synovial fluid filtration and synovial gel formation at normal approach of cartilage surfaces in the human synovial joints loaded by a compressive force has been recently presented in Parts I and II of this paper (Hlavacek, 1993, J. Biomechanics 26, 1145–1150; 1151–1160). In the model synovial fluid is taken as a mixture of two incompressible fluids (ideal and Newtonian viscous), while the biphasic model of Mow et al. (1980, J. Biomech. Engng 102, 73–84) is used for cartilage. A system of partial differential equations for the normal approach of axially symmetric cartilage surfaces in the human hip joint obtained in Part II is solved numerically for low loads. A shallow pocket-type configuration of the synovial film is formed shortly after the load application at time t = 0. For constant loads the fluid film pressure profile follows very closely that in a dry frictionless contact. To this approximation and with the exception of a close vicinity of the squeeze-film edge the flux of the ideal fluid across the synovial fluid-cartilage interface varies quadratically with the radial distance r and decreases as t −1 2 with time. The ideal fluid is forced into cartilage at the central region and out of cartilage at the low-pressure periphery of the squeezed synovial film. The maximum gel-forming concentration (the 20-fold of the original value) of the hyaluronic acid-protein macromolecular complex of the synovial fluid is reached at the film centre first, then the gel film starts spreading quickly sideways. Later, the process slows down approaching the value r 2 1 2 where r is the radius of a dry frictionless contact. The final gel-film thickness decreases very slowly with the increasing r for 0 ≤ r r 2 1 2 .

Summary Antibodies to heat shock proteins of the 65 kDa group were demonstratedin canine sera and synovial fluid. This paper reports these antibody measurements in three groups of dogs with joint disease and compares them with those of a control population. Dogs with rheumatoid arthritis (RA) showed higher anti-heat shock proteins (HSP) antibody levels, in both their sera and synovial fluids, compared to the control dogs and these antibodies were predominantly of the IgG and IgM class; there was a significant correlation between IgM anti-HSP65 and IgM-rheumatoid factors. There was also a significant correlation between anti-HSP65 and antibodies to canine distemper virus, but only of the IgM class and the relevance of these antibodies to the overall pathogenesis of canine RA and, in particular, to the presence of canine distemper virus within the joint, are discussed.

This paper reviews, in a first part, methods used for the clinical assessment of osteoarthritis (OA) with special reference, in a second part, to trials of drugs claimed to be chondromodulating agents. The agents examined include glycosaminoglycan-peptide complex (GP-C, Rumalon) and glycosaminoglycan-polysulfate (GAGPS, Arteparon), which both showed some beneficial clinical response. However, their effect on cartilage still remains controversial. The development of a functional hip and knee OA index in clinical assessment and the role of imaging methods and biochemical markers are discussed. In future clinical trials only validated OA indices such as the Lequesne or WOMAC index and the newly established ILAR guidelines for classifying and testing drugs in OA will be accepted for registration purposes. Imaging methods including magnetic resonance imaging (MRI) offer the capacity to provide more precise information concerning cartilage destruction in OA joints. In addition, the biochemical assessment of proteoglycan fragments, bone sialoprotein (BSP), cartilage oligometric matrix protein (COMP) and the balance between stromelysin and its inhibitor (TIMP) in synovial fluid would appear to offer potential applications for the determination of joint tissue damage in the early and later stages of OA. However, these biochemical markers have yet to be validated. It is clear that in the 1990s, for a drug to be designated as disease modifying in OA, it will require a more rigorous evaluation than was hitherto required.

Objective. A unified mathematical model of two different modes of inception of fissures at the surface of articular cartilage in healthy and pathological joints. Design. The superficial tangential zone of articular cartilage is modeled as a three-phase medium consisting of collagen fibers, matrix, and of infiltrated thin constituent of synovial fluid. Background. The author’s general mesomechanical concept is applied to the analysis of deterioration of articular cartilage. Methods. Theoretical analysis based on the results of the author’s preceding paper. Results. The presented analysis shows that superficial fissures in articular cartilage can also be caused by pathological thinning of synovial fluid. Conclusions. Whereas in healthy joints the probable cause of creation of fissures at the surface of cartilage was shown to be fast impact loading, in joints with inflammatory synovial fluid the fissures can be caused by plain walking. Relevance Appearance of surface fissures in articular cartilage is a serious, still not fully clarified problem that deserves attention.

A mathematical model of synovial film filtration and synovial gel formation at normal approach of cartilage surfaces in the human hip joint is presented. The biphasic mixture model presented in Part I of this paper [Hlavácek, J. Biomechanics 26, (1993)] for synovial fluid and that of Mow and his collaborators [J. Biomech. Engng 102, 73-84 (1980)] for cartilage are used. A general analysis of filtration of an axially symmetric synovial squeeze-film between two cartilage layers at normal approach is given. The geometrically simple case much idealising the human hip joint is also considered: two cartilage discs with a synovial film in between are compressed by the steady loading of the half human weight. The homogeneous film filtration process where the synovial gap remains parallel and the macromolecular concentration in the gap is spatial homogeneous (to the thin-film approximation) and time-dependent is numerically analysed. If the hyaluronic acid concentration of the synovial gel at equilibrium is 50 mg/ml at least, the resulting stable gel layer thickness for the homogeneous filtration in the human hip joint and for normal synovial fluids is about 0.1 micron, being almost independent of the loading. Inflammatory synovial fluid shows values several times lower.

The pyridinium crosslinks are important biomarkers of mature hard tissue collagen degradation. This paper describes an isocratic ion-paired reversed-phase high-performance chromatographic assay using narrow-bore columns and high-sensitivity fluorescence detection to enable for the first time the determination of pyridinium crosslinks in both serum and synovial fluid samples. Extracted freeze-dried acid hydrolysates were re-suspended in 20 mM pentafluoropropionic acid (PFPA). Separations were carried out using an Exsil 100 5-μm ODS2 column (100 mm × 2.1 mm I.D.) eluted with 10 mM PFPA in water at 0.15 ml/min and detected using a Jasco 821-FP detector (xenon lamp: excitation 290 nm, emission 400 nm). Fluorescent response was linear from 269 to 8620 fmol for pyridinoline (Pyr) and 85 to 2710 fmol for deoxypyridinoline (dPyr). The limits of detection were 28 and 57 fmol, respectively. The coefficient of variation for extraction and analysis of normal serum was 7.96% for Pyr and 6.30% for dPyr (n = 6). The mean ± S.D. concentration of Pyr in normal serum was 3.26 ± 0.83 nM.

Oligomers of prostaglandin B 1 inhibited phospholipase A 2 extracted from human neutrophils in a dose-dependent manner (IC 50 = 5 μM), while the monomer was not inhibitory at concentrations of 10 μM or less. The inhibitory activity of PGB 1 oligomers increased with increasing polymer size; PGB dimer had approximately one-half the maximal inhibitory activity of PGBx, while a trimer was almost as inhibitory as a tetramer and PGBx ( n = 6). PGBx as an oil or as a water-soluble sodium-salt-inhibited Ca 2+ -dependent phospholipase A 2 from snake venom, bovine pancreas, human neutrophil and platelet, human synovial fluid, and human sperm with IC 50 values ranging from 0.5–7.5 μM. Inhibition was independent of added Ca 2+ and was independent of substrate phospholipid concentration. Interaction of purified snake venom phospholipase A 2 ( Naja mocambique ) with PGBx resulted in dose-dependent quenching of the enzyme's tryptophan fluorescence; 50% quench was noted with a molar ratio of PGBx/enzyme of 1.5. Inhibition of phospholipase A 2 activity by PGBx was relieved in a dose-dependent manner by either defatted or untreated bovine serum albumin. PGBx is a potent in vitro inhibitor of a wide spectrum of phospholipases A 2 , and as illustrated in the accompanying paper, has profound inhibitory effects on arachidonic acid mobilization in human neutrophils and vascular endothelial cells. Modulation of cellular and extracellular phospholipases A 2 , and the bioactive transmitters generated by this catalytic event, may be a basic mechanism by which oligomers of prostaglandin B 1 exert their reported membrane-protective effects.

Aged articular cartilage has no other means of nutritional transport to the cartilage cells except the inbuilt mechanism of interstitial fluid exchange in between the cartilage and synovial fluid. The secreted nutrition from blood mixes well in the synovial fluid and during articulation it enters into the cartilage where it meets with the cartilage cells. The local variation of the permeability of the cartilage, therefore, plays a very important role in the whole mechanism. Analytically the problem is formulated as a two region diffusion and flow model: flow and diffusion in between two approaching cartilage surfaces and within the porous cartilages. The solution of the coupled mixed boundary value problem could only be obtained for a few particular cases. It has been observed that the increased permeability at the surface does not allow nutrition to the cells in the deeper region and they die out. In case of diseased joints the nutritional transport is very difficult owing to increased rigidity or local variation of permeability within the cartilage. The paper further concludes that for low molecular weight solutes, the phenomenon of nutritional transport is diffusion dominated whereas for large molecular weight solutes, it is dominated by mechanical pumping action.

The diagnosis of gout and pseudogout has traditionally been established by the identification, in synovial fluid, of monosodium urate and calcium pyrophosphate dihydrate crystals with compensated polarizing light microscopy. In this paper the utility of electron microscopy in establishing these diagnosis in two cases, when the conventional means of synovial fluid analysis had failed to do so, is discussed. The application of ultrastructural analysis of synovial fluid increases diagnostic capability in the crystal deposition diseases, and it is recommended for those patients in whom the more usual studies have not established a diagnosis.

This paper describes a model of two parallel plates with reference to load bearing human joints. The lower plate is porous and consists of three layers of different porosities. The lubricant (synovial fluid) is represented by a micropolar fluid. The results are obtained for pressure, load capacity and time of approach. Variation of pressure and load capacity with the variation of porosity in the upper layer is also discussed. Effects of size and concentration variation of the hyaluronic acid molecules on the mechanism of synovial joint have been investigated in the standing position.

FORMERLY untouchable human joints are now receiving the attention of workers in widely separated fields. This is not surprising for there has been a growing realization that in the synovial joint, biochemistry, anatomy and mechanics converge and influence each other in many direct and intimate ways. A movable joint is composed of the synovial membrane and capsule, articular cartilage and subchondral bone, ligaments, tendons and fibrocartilages, and synovial fluid. The most urgent need has been a means to obtain specimens of these joint components from living subjects. This need was perhaps first met by the introduction of safe and effective needles [24] that permitted biopsies of synovial membrane from closed joints of ambulatory patients. Specimens of synovial membrane, cartilage, or bone are now obtained with increasing frequency by orthopedic surgeons during arthrotomy [5, 61, or from amputated limbs [7]. A great deal of information is accumulating from studies on joint components using techniques of chemistry, immunology, histology, cytochemistry, electron microscopy, and immunohistology. Integration and synthesis of this information into a coherent view of joint function is making progress, especially in the normal joint [8, 91. New studies and ideas relate the structure and metabolism of the synovial membrane to its secretion of synovial fluid, and explore the function of this viscous fluid as a nutrient source and lubricant for the moving articular cartilages. This paper will concentrate on some aspects of the altered structure and function of synovial joints involved by rheumatoid arthritis.