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At least 1,135 records · Page 63Linked to original sources
PubMed2001

How severe must repetitive loading be to kill chondrocytes in articular cartilage?

OBJECTIVE: Little is known about the effects of severe repetitive loading on articular cartilage chondrocytes, even though epidemiological studies associate this type of loading with osteoarthritis. We hypothesize that repetitive loading can kill cartilage chondrocytes in a dose-related manner. DESIGN: Large cartilage-on-bone specimens were cut from the patella groove of bovine knees obtained directly from a slaughterhouse. Cartilage was loaded using a flat impermeable indenter in such a manner that the loaded region was supported naturally by surrounding cartilage and subchondral bone. Specimens received 3600 cycles of compressive loading at 1 Hz, with the peak load lying in the range 1-70% of the force required to damage cartilage in a single loading cycle (35 MPa). Cell viability was assessed in thick sections of loaded and control cartilage using a paravital staining method: fluorescein diacetate stained live cells green, and propidium iodide stained dead cells red. The assay was validated on cartilage which had been subjected to repeated freeze-thaw cycles to kill the chondrocytes. RESULTS: Paravital staining revealed 100% cell death after one freeze-thaw cycle at -196 degrees C and three cycles at -20 degrees C. Baseline chondrocyte viability was 80% in unloaded cartilage, and viability decreased when applied compressive loading exceeded 6 MPa. Above this threshold, cell viability was inversely proportional to applied stress. When gross damage to the cartilage surface first became evident, above 14 MPa, 40% of cells remained viable. Load-induced chondrocyte death was greatest in the surface zone, and extended beyond the loaded area. Electron micrographs indicated that some cells were dying by apoptosis. CONCLUSIONS: Some chondrocytes are much more vulnerable to repetitive mechanical loading than others, suggesting that vigorous activity may lead to cell death in articular cartilage.

Animals↗
PubMed2002

Differential responses of chondrocytes from normal and osteoarthritic human articular cartilage to mechanical stimulation.

Mechanical stimulation is critically important for the maintenance of normal articular cartilage integrity. Molecular events regulating responses of chondrocytes to mechanical forces are beginning to be defined. Chondrocytes from normal human knee joint articular cartilage show increased levels of aggrecan mRNA following 0.33 Hz mechanical stimulation whilst at the same time relative levels of MMP3 mRNA are decreased. This anabolic response, associated with membrane hyperpolarisation, is activated via an integrin-dependent interleukin (IL)-4 autocrine/paracrine loop. Work in our laboratory suggests that this chondroprotective response may be aberrant in osteoarthritis (OA). Chondrocytes from OA cartilage show no changes in aggrecan or MMP3 mRNA following 0.33 Hz mechanical stimulation. alpha5beta1 integrin is the mechanoreceptor in both normal and OA chondrocytes but downstream signalling pathways differ. OA chondrocytes show membrane depolarisation following 0.33 Hz mechanical stimulation consequent to activation of an IL1beta autocrine/paracrine loop. IL4 signalling in OA chondrocytes is preferentially through the type I (IL4alpha/cgamma) receptor rather than via the type II (IL4alpha/IL13R) receptor. Altered mechanotransduction and signalling in OA may contribute to changes in chondrocyte behaviour leading to increased cartilage breakdown and disease progression.

Aggrecans↗
PubMed2004

Do changes in the mechanical properties of articular cartilage promote catabolic destruction of cartilage and osteoarthritis?

Osteoarthritis (OA) is a joint disease characterized by cartilage degeneration, a thickening of subchondral bone, and formation of marginal osteophytes. Previous mechanical characterization of cartilage in our laboratory suggests that energy storage and dissipation is reduced in osteoarthritis as the extent of fibrillation and fissure formation increases. It is not clear whether the loss of energy storage and dissipation characteristics is a result of biochemical and/or biophysical changes that occur to hyaline cartilage in joints. The purpose of this study is to present data, on the strain rate dependence of the elastic and viscous behaviors of cartilage, in order to further characterize changes that occur in the mechanical properties that are associated with OA. We have previously hypothesized that the changes seen in the mechanical properties of cartilage may be due to altered mechanochemical transduction by chondrocytes. Results of incremental tensile stress-strain tests at strain rates between 100%/min and 10,000%/min conducted on OA cartilage indicate that the slope of the elastic stress-strain curve increases with increasing strain rate, unlike the reported behavior of skin and self-assembled collagen fibers. It is suggested that the strain-rate dependence of the elastic stress-strain curve is due to the presence of large quantities of proteoglycans (PGs), which protect articular cartilage by increasing the apparent stiffness. The increased apparent stiffness of articular cartilage at high strain rates may limit the stresses borne and prolong the onset of OA. It is further hypothesized that increased compressive loading of chondrocytes in the intermediate zone of articular cartilage occurs as a result of normal wear to the superficial zone or from excessive impact loading. Once the superficial zone of articular cartilage is worn away, the tension is decreased throughout all cartilage zones leading to increased chondrocyte compressive loading and up-regulation of mechanochemical transduction processes that elaborate catabolic enzymes.

Aged↗
PubMed2002

Aging, articular cartilage chondrocyte senescence and osteoarthritis.

The incidence of osteoarthritis (OA), the disease characterized by joint pain and loss of joint form and function due to articular cartilage degeneration, is directly correlated with age. The strong association between age and increasing incidence of osteoarthritis (OA) marks OA as an age related disease. Yet, like many other age related diseases, OA is not an inevitable consequence of aging; instead, aging increases the risk of OA. Articular cartilage aging changes that may lead to articular cartilage degeneration include fraying and softening of the articular surface, decreased size and aggregation of proteoglycan aggrecans and loss of matrix tensile strength and stiffness. These changes most likely are the result of an age related decrease in the ability of chondrocytes to maintain and repair the tissue manifested by decreased mitotic and synthetic activity, decreased responsiveness to anabolic growth factors and synthesis of smaller less uniform aggrecans and less functional link proteins. Our recent work suggests that progressive chondrocyte senescence marked by expression of the senescence associated enzyme beta-galactosidase, erosion of chondrocyte telomere length and mitochondrial degeneration due to oxidative damage causes the age related loss of chondrocyte function. New efforts to prevent the development and progression of OA might include strategies that slow the progression of chondrocyte senescence or replace senescent cells.

Aging↗
PubMed2001

Biphasic poroviscoelastic simulation of the unconfined compression of articular cartilage: II--Effect of variable strain rates.

This study investigated the abilities of the linear biphasic poroviscoelastic (BPVE) model and the linear biphasic poroelastic (BPE) model to simulate the effect of variable ramp strain rates on the unconfined compression stress relaxation response of articular cartilage. Curve fitting of experimental data showed that the BPVE model was able to successfully account for the ramp strain rate-dependent viscoelastic behavior of articular cartilage under unconfined compression, while the BPE model was able to account for the complete viscoelastic response at a slow strain rate, but only the long-term viscoelastic response at faster strain rates. We concluded that the short-term viscoelastic behavior of articular cartilage, when subjected to a fast ramp strain rate, is primarily governed by a fluid flow-independent (intrinsic) viscoelastic mechanism, whereas the long-term viscoelastic behavior is governed by a fluid flow-dependent (biphasic) viscoelastic mechanism. Furthermore, a linear viscoelastic representation of the solid stress was found to be a valid model assumption for the simulation of ramp strain rate-dependent relaxation behaviors of articular cartilage within the range of ramp strain rates investigated.

Animals↗
PubMed1987

[Initial degeneration of the articular cartilage in the rat].

The authors have investigated the process of degeneration of articular cartilage in its early stages using an experimental model which has made it possible to show, for the first time, the effects of a mechanical parameter other than excessive pressure--that is excessive friction. The two healthy hips in twenty anaesthetised young rats were used for the study. One hip was kept immobile and served as a control. The other was subjected to physiological movements of flexion and extension continuously and without rest for periods varying from twelve hours to seven days. The articular cartilage of the two femoral heads was examined by light microscopy, transmission electron microscopy and scanning electron microscopy. A new fact was demonstrated. Cartilage wear is also associated with the simple movement of two joint surfaces over one another without any muscle contraction being involved. In the genesis of cartilage wear, excessive friction alone seems to be as important as excessive pressure.

Aging↗
PubMed1976

[Homologous articular cartilage transplantation in animal experiments. Preliminary studies on sheep (author's transl)].

Homologous articular cartilage without subchondral bone instead of the usual osteochondral grafts was transplanted in sheep. The transplants were fixed to the host by a biological tissue adhesive based on fibrinogen clotting. Light- and electronmicroscopic studies showed viable transplants up to 7 months and a stable bony union with the host through endochondral bone formation. A additional external fixation of the joint after transplantation or the use of a conventional cyanoacrylate tissue adhesive failed to achieve positive results. The relations of these preliminary findings for restorative techniques of articular cartilage defects are discussed.

Animals↗
PubMed2001

The state of the articular cartilage at the time of surgery as an indication for rotational acetabular osteotomy.

We have studied whether the state of the articular cartilage at the time of rotational acetabular osteotomy for dysplasia of the hip affects the outcome 2 to 5.5 years after surgery. Arthroscopy in 57 patients (59 joints) at the time of the operation showed grade-0 changes in seven, grade-1 in nine, grade-2 in 17, grade-3 in 14 and grade-4 in 12 joints, according to the classification of Outerbridge. There was radiological evidence of the progression of arthritis in four joints which were classified at arthroscopy as grade 4. Stepwise regression analysis showed that damage to acetabular or femoral articular cartilage significantly affected the progression of arthritis. We conclude that the short-term results of successful rotational acetabular osteotomy for dysplasia are affected by the state of the articular cartilage.

Acetabulum↗
PubMed1997

A theoretical formulation for boundary friction in articular cartilage.

A theoretical boundary friction model is proposed for predicting the frictional behavior of articular cartilage, including its time-dependent, velocity-dependent, and load-dependent responses. This theoretical model uses the framework of the biphasic theory for articular cartilage, and provides a mathematical formulation for the principle that interstitial fluid pressurization contributes significantly to reduction of the effective friction coefficient. Several examples of the application of this theory are provided, which demonstrate that a variety of experimentally observed cartilage frictional behaviors can now be theoretically predicted.

Cartilage, Articular↗
PubMed1998

Fast spin-echo MR of the articular cartilage in the osteoarthrotic knee. Correlation of MR and arthroscopic findings.

PURPOSE: The objective was to assess the efficacy of fast spin-echo (FSE) imaging in the detection of articular cartilage abnormality in osteoarthrosis of the knee. MATERIAL AND METHODS: We studied 356 articular surfaces in 73 knees that had been examined by both MR imaging and arthroscopy. The MR images were obtained with FSE imaging (TR/TE 4200/100) on a 0.5 T unit. The surface abnormalities of the articular cartilage that were detected by MR imaging were compared with the arthroscopic findings. RESULTS: The overall sensitivity and specificity of MR in detecting chondral abnormalities were 60.5% (158/261) and 93.7% (89/95) respectively. MR imaging was more sensitive to the higher grade lesions: 31.8% (34/107) in grade 1; 72.4% (71/98) in grade 2; 93.5% (43/46) in grade 3; and 100% (10/10) in grade 4. The MR and arthroscopic grades were the same in 46.9% (167/356), and differed by no more than 1 grade in 90.2% (321/356) and 2 grades in 99.2% (353/356). The correlation between arthroscopic and MR grading scores was highly significant with a correlation coefficient of 0.705 (p < 0.0001). CONCLUSION: FSE sequence was less sensitive to mild cartilage abnormality but useful in detecting moderate to severe abnormality and in evaluating the degree of articular cartilage abnormality.

Adult↗
PubMed1992

Mechanism of catabolism of aggrecan by articular cartilage.

Characterization of aggrecan core protein peptides appearing in the medium of adult articular cartilage maintained in tissue culture showed that eight major peptides could be detected. The two largest peptides had the same N-terminal sequence as bovine aggrecan core protein and probably represent partly degraded aggrecan lost to the medium in the form of the proteoglycan aggregate. The three next smallest peptides were all shown to have another N-terminal sequence which corresponded to a sequence in the interglobular domain starting at alanine residue 393 of the human aggrecan core protein (K. Doege et al., 1991, J. Biol. Chem. 266, 894-902). Two other peptides were isolated and shown to have two different N-terminal amino sequences corresponding to sequences in the chondroitin sulfate attachment domain 2 of the core protein starting at alanine residue 1839 and leucine residue 1939 of human aggrecan. This suggests that the catabolism of aggrecan by adult articular cartilage occurs by the proteolytic cleavage of the core protein of this proteoglycan at three separate sites. Examination of the amino acid sequences around each of these cleavage sites showed a similar pattern TEGE decreases ARGS, TAQE decreases AGEG, and VSQE decreases LGQR, suggesting that a single proteinase may be involved in the catabolism of aggrecan. Analysis of synovial fluids and serum of age-matched animals revealed the presence of aggrecan core protein peptides corresponding in size to those detected in vitro, thus indicating the cleavage observed in explant culture is the same as that which occurs in vivo.

Aggrecans↗
PubMed2006

Collagen network of articular cartilage modulates fluid flow and mechanical stresses in chondrocyte.

The extracellular matrix of articular cartilage modulates the mechanical signals sensed by the chondrocytes. In the present study, a finite element model (FEM) of the chondrocyte and its microenvironment was reconstructed using the information from fourier transform infrared imaging spectroscopy. This environment consisted of pericellular, territorial (mainly proteoglycans), and inter-territorial (mainly collagen) matrices. The chondrocyte, pericellular, and territorial matrix were assumed to be mechanically isotropic and poroelastic, whereas the inter-territorial matrix, due to its high collagen content, was assumed to be transversely isotropic and poroelastic. Under instantaneous strain-controlled compression, the FEM indicated that the fluid pressure within the chondrocyte increased nonlinearly as a function of the in-plane Young's modulus of the collagen network. Under instantaneous force-controlled compression, the chondrocyte experienced the highest fluid pressure when the in-plane Young's modulus of the collagen network was approximately 4 MPa. Based on the present results, the mechanical characteristics of the collagen network of articular cartilage can modify fluid flow and stresses in chondrocytes. Therefore, the integrity of the collagen network may be an important determinant in cell stimulation and in the control of the matrix maintenance.

Biophysical Phenomena↗
PubMed1987

Nonsteroidal antiinflammatory drugs and articular cartilage.

Salicylates and some other nonsteroidal antiinflammatory drugs (NSAID) suppress proteoglycan biosynthesis in normal articular cartilage in vitro. Their effect on osteoarthritic cartilage in vitro is even greater than their effect on normal cartilage. Aspirin has a similar effect in vivo on both atrophic cartilage and osteoarthritic cartilage in the dog, although no in vivo effect of salicylate on normal joint cartilage has been observed. While the magnitude of the effects of NSAID on proteoglycan metabolism in cartilage appeared to be inversely related to the proteoglycan content of the matrix, it is possible that some drugs are selectively bound to cartilage matrix components, which could affect their action on the chondrocyte. If NSAID have similar effects in patients with arthritis, this could have implications with respect to articular cartilage lesions.

Animals↗
PubMed1993

Versican gene expression in human articular cartilage and comparison of mRNA splicing variation with aggrecan.

The chondrocytes in human articular cartilage from subjects of all ages express mRNAs for both of the aggregating proteoglycans aggrecan and versican, although the level of expression of versican mRNA is much lower than that of aggrecan mRNA. Aggrecan shows alternative splicing of the epidermal growth factor (EGF)-like domain within its C-terminal globular region, but there is no evidence for a major difference in situ in the relative expression of this domain with age. At all ages studied from birth to the mature adult, a greater proportion of transcripts lacked the EGF domain. The relative proportions of the two transcripts did not change upon culture and passage of isolated chondrocytes. In contrast, the neighbouring complement regulatory protein (CRP)-like domain was predominantly expressed irrespective of age, but cell culture did result in variation of the splicing of this domain. Versican possesses two EGF-like domains and one CRP-like domain, but at all ages the three domains were predominantly present in all transcripts. This situation persisted upon culture and passage of the chondrocytes. Thus, unlike aggrecan, the versican expressed by human articular cartilage does not appear to undergo alternative splicing of its C-terminal globular region, either in cartilage in situ or in chondrocytes in culture.

Adult↗
PubMed1996

Resurfacing of goat articular cartilage by chondrocytes derived from bone marrow.

The feasibility of using cartilaginous implants containing bone marrow derived chondrocytes in biological resurfacing procedures for correcting defects in articular cartilage was examined in goats. The experimental protocol included bone marrow aspiration, mesenchymal cell culturing, cell proliferation, favorable conditions inducing chondrogenic differentiation, and implantation of autogeneic and allogeneic cells. Autogeneic implant transplantations proved to be the best source for regeneration and repair of defective articular surfaces with use of densitometric computed image analysis of histochemical and immunohistochemical parameters on tissue sections. Allogeneic chondrocyte enriched cultures derived from bone marrow evoke a typical immune response in the host, expressed by the formation of fibrosis and progressive joint arthrosis. In the current study, a biological resurfacing procedure is described in detail for large mammals of similar weight and size as humans. Autogeneic mesenchymal cells derived from a bone marrow aspiration are the best cell source and when embedded in hyaluronic acid based adhesive glue make an excellent cartilaginous implant. The reparative regenerated cartilaginous tissue outcome within the defects appear different than neighboring normal articular cartilage shortly after surgery. Whether in the long term the cartilaginous remodeling process will shape the cartilage such that it more closely resembles the original articular cartilage is not known.

Animals↗
PubMed2001

Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo.

Overexpression of interleukin (IL-)17 has recently been shown to be associated with a number of pathological conditions. Because IL-17 is found at high levels in the synovial fluid surrounding cartilage in patients with inflammatory arthritis, the present study determined the direct effect of IL-17 on articular cartilage. As shown herein, IL-17 was a direct and potent inducer of matrix breakdown and an inhibitor of matrix synthesis in articular cartilage explants. These effects were mediated in part by leukemia inhibitory factor (LIF), but did not depend on interleukin-1 activity. The mechanism whereby IL-17 induced matrix breakdown in cartilage tissue appeared to be due to stimulation of activity of aggrecanase(s), not matrix metalloproteinase(s). However, IL-17 upregulated expression of matrix metalloproteinase(s) in chondrocytes cultured in monolayer. In vivo, IL-17 induced a phenotype similar to inflammatory arthritis when injected into the intra-articular space of mouse knee joints. Furthermore, a related protein, IL-17E, was found to have catabolic activity on human articular cartilage. This study characterizes the mechanism whereby IL-17 acts directly on cartilage matrix turnover. Such findings have important implications for the treatment of degenerative joint diseases such as arthritis.

Animals↗
PubMed1987

Preparative electrophoresis on agarose submerged gels of two aggregating proteoglycan monomers from articular cartilage.

Analytical electrophoresis on polyacrylamide-agarose gels of aggregating proteoglycan monomers from baboon articular cartilage produces two distinct bands, corresponding to two different aggregating monomer populations. A preparative electrophoresis procedure is described for isolating the two monomers. Proteoglycans were extracted from young baboon articular cartilage in 4 M guanidinium chloride containing proteolysis inhibitors and aggregated after hyaluronic acid addition. The aggregates were separated from non-aggregated proteoglycans by isopycnic centrifugation, followed by gel chromatography on Sepharose CL-2B. The monomers of the aggregates were obtained by isopycnic centrifugation under dissociative conditions. Two monomers were separated by preparative electrophoresis on 0.8 % agarose submerged gels. Approximately 60 % of the proteoglycans were recovered from the gel using a freeze-squeeze procedure. Aliquots of the separated monomers gave single bands when submitted to analytical polyacrylamide-agarose gel electrophoresis. Their migration and appearance were similar to that of the two bands present in the non separated preparation of monomers.

Animals↗
PubMed1981

Age-related changes in the chemical composition of bovine articular cartilage. The structure of high-density proteoglycans.

Proteoglycans were extracted from the articular cartilage of foetal, calf and adult bovine metacarpal-phalangeal joints with 4m-guanidinium chloride. After extraction, the high-density proteoglycans (PG-I fractions) were prepared by sedimentation in two sequential CsCl-density-gradient procedures [Swann, Powell & Sotman (1979) J. Biol. Chem.254, 945-954]. The PG-I fractions from foetal, calf and adult tissues accounted for 75%, 52% and 46% respectively of the extracted components. The glucosamine, galactose, N-acetylneuraminic acid and protein contents increased with age. The overall amino acid compositions of PG-I fractions were similar. Fractionation of PG-I-fraction samples on a Bio-Gel A-50m column indicated that the molecular weight decreased with age. The PG-I fractions were specifically (3)H-labelled by treatment with galactose oxidase followed by reduction with NaB(3)H(4). The (3)H radioactivity was incorporated into both galactose and galactosamine residues of different carbohydrate side chains. The elution profiles of alkaline borohydride-treated foetal, calf and adult PG-I-fraction samples on a Sepharose 6B column showed that the molecular weights of chondroitin sulphate chains were 13500, 12000 and 10500 in foetal, calf and adult tissues respectively. Fractionation of the alkaline borohydride-treated foetal, calf and adult PG-I-fraction samples and (3)H-labelled calf and adult PG-I-fraction samples on a Bio-Gel P-10 column showed that there was an inverse relationship between the low-molecular-weight O-linked oligosaccharides and the higher-molecular-weight sialic acid-containing constituents at different ages. The oligosaccharide components of foetal, calf and adult PG-I-fraction samples represented 79%, 69% and 36% respectively of the total sialic acid content of the proteoglycans. Similarly in the (3)H-labelled calf and adult samples 75% and 30% of the total radioactivity were present in the oligosaccharide components respectively. Digestion with chondroitinase AC-II and infrared analyses showed that the PG-I-fraction F and C samples contained primarily chondroitin 4-sulphate chains whereas PG-I-fraction sample A was 6-sulphated. These studies show that the major proteoglycans (PG-I fractions) in the articular cartilage of foetal, calf and adult animals differ in the content, types and structure of the chondroitin sulphate, keratan sulphate and oligosaccharide constituents. These changes in proteoglycan structure reflect the gross age-related changes in the chemical composition of the tissue.

Aging↗