Biorheology - Volume 39, issue 1-2

Authors: Li, LePing | Buschmann, M.D. | Shirazi‐Adl, A.

Article Type: Research Article

Abstract: Collagen fibril reinforcement was incorporated into a nonlinear poroelastic model for articular cartilage in unconfined compression. It was found that the radial fibrils play a predominant role in the transient mechanical behavior but a less important role in the equilibrium response of cartilage. The radial fibrils are in tension and can be highly stressed during compression, in contrast to low compressive stresses in all directions for the proteoglycan matrix after a small initial compression. The strain dependent fibril stiffening produces strong nonlinear transient response; the fibrils provide extra stiffness to balance a rising fluid pressure and to restrain stress increase …in the proteoglycans. The fibril reinforcement, induced by the fluid pressure and flow, also accounts for a complex pattern of strain‐magnitude and strain‐rate dependence of cartilage stiffness. Show more

Keywords: Cartilage mechanics, fibril reinforcement, finite element, poroelasticity, strain rate

Citation: Biorheology, vol. 39, no. 1-2, pp. 89-96, 2002

Authors: Salter, D.M. | Millward‐Sadler, S.J. | Nuki, G. | Wright, M.O.

Article Type: Research Article

Abstract: 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. α5β1 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 IL1β autocrine/paracrine loop. IL4 signalling in OA chondrocytes is preferentially through the type I (IL4α/cγ) receptor rather than via the type II (IL4α/IL13R) receptor. Altered mechanotransduction and signalling in OA may contribute to changes in chondrocyte behaviour leading to increased cartilage breakdown and disease progression. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 97-108, 2002

Authors: Sironen, Reijo K. | Karjalainen, Hannu M. | Törrönen, Kari | Elo, Mika A. | Kaarniranta, Kai | Takigawa, Masaharu | Helminen, Heikki J. | Lammi, Mikko J.

Article Type: Research Article

Abstract: Hydrostatic pressure has a profound effect on cartilage tissue and chondrocyte metabolism. Depending on the type and magnitude of pressure various responses can occur in the cells. The mechanisms of mechanotransduction at cellular level and the events leading to specific changes in gene expression are still poorly understood. We have previously shown that induction of stress response in immortalized chondrocytes exposed to high static hydrostatic pressure increases the stability of heat shock protein 70 mRNA. In this study, our aim was to examine the effect of high pressure on gene expression profile and to study whether stabilization of mRNA molecules …is a general phenomenon under this condition. For this purpose a cDNA array analysis was used to compare mRNA expression profile in pressurized vs. non‐pressurized human chondrosarcoma cells (HCS 2/8). mRNA stability was analyzed using actinomycin‐treated and nontreated samples collected after pressure treatment. A number of immediate‐early genes, and genes regulating cell cycle and growth were up‐regulated due to high pressure. Decrease in osteonectin, fibronectin, and collagen types VI and XVI mRNAs was observed. Also bikunin, cdc37 homologue and Tiam1, genes linked with hyaluronan metabolism, were down‐regulated. In general, stability of down‐regulated mRNA species appeared to increase. However, no increase in mRNA above control level due to stabilization was noticed in the genes available in the array. On the other hand, mRNAs of certain immediate‐early genes, like c‐jun, jun‐B and c‐myc, became destabilized under pressure treatment. Increased accumulation of mRNA on account of stabilization under high pressure conditions seems to be a tightly regulated, specific phenomenon. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 111-117, 2002

Authors: Loeser, Richard F.

Article Type: Research Article

Abstract: Integrins are adhesion receptor heterodimers that transmit information from the extracellular matrix (ECM) to the cell through activation of cell signaling pathways. Chondrocytes express several members of the integrin family including α5 β1 which is the primary chondrocyte receptor for fibronectin. Cell signaling mediated through integrins regulates several chondrocyte functions including differentiation, matrix remodeling, responses to mechanical stimulation and cell survival. Integrin‐mediated activation of members of the mitogen‐activated protein kinase family likely plays a key role in transmitting signals regulating chondrocyte gene expression. Upstream mediators of mitogen‐activated protein kinase (MAP kinase) activation include focal adhesion kinase (FAK) and proline‐rich …tyrosine kinase 2 (pyk2) which are both expressed by chondrocytes. A better understanding of chondrocyte integrin signaling is needed to define the mechanisms by which the ECM regulates chondrocyte function. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 119-124, 2002

Authors: Westacott, C.I. | Urban, J.P.G. | Goldring, M.B. | Elson, C.J.

Article Type: Research Article

Abstract: This work was performed to determine whether one aspect of load, pressure, could alter tumour necrosis factor (TNF) receptor type I (RI) expression on chondrocytes. Encapsulated tsT/AC62, osteoarthritic (OA) or non‐arthritic (NA) chondrocytes were centrifuged at speeds representing 5 or 20 MPa, incubated for specific periods, released from alginate and TNFRI and II (TNFRII) expression determined by flow cytometry. Significant (p<0.05, n=4) changes in tsT/AC62 chondrocyte TNFRI expression were apparent 24 hours after application of 20 MPa. Five or 20 MPa increased OA chondrocyte TNFRI expression; chondrocytes from some OA patients were markedly sensitive to 20 MPa. NA chondrocyte TNFRI …expression usually decreased in response to 5 and 20 MPa. Significant pressure‐induced differences in TNFRI expression between NA and OA groups were apparent at 5, but not 20 MPa. Pressure did not significantly alter TNRFII expression on tsT/AC62, NA or OA chondrocytes. These results suggest a mechanism whereby sensitivity of chondrocytes to the effects of TNFα may be increased, in susceptible individuals, in regions of the joint that experience peak loading. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 125-132, 2002

Authors: Lee, R.B. | Wilkins, R.J. | Razaq, S. | Urban, J.P.G.

Article Type: Research Article

Abstract: Cartilage is routinely subjected to varying mechanical stresses which are known to affect matrix turnover by a variety of pathways. Here we show that mechanical loads which suppress sulphate incorporation or protein synthesis by articular chondrocytes, also inhibit rates of oxygen uptake and of lactate production. Although the mechanisms have not been definitively identified, it has been shown that high hydrostatic pressures reduce the activity of the glucose transporter GLUT. Furthermore, fluid expression consequent on static loading changes intracellular pH and ionic strength; intracellular changes which would reduce the activity of glycolytic enzymes. Both pathways would thus lead to a …fall in rates of glycolysis and a reduction in intracellular ATP, and – since ATP concentrations directly affect sulphation of proteoglycans – a rapid fall in sulphate incorporation. Our results suggest that load‐induced changes in matrix synthesis in cartilage can occur by means other than changes in gene expression. Show more

Keywords: Proteoglycan, ATP, lactate, oxygen, GLUT, MCT

Citation: Biorheology, vol. 39, no. 1-2, pp. 133-143, 2002

Authors: Martin, James A. | Buckwalter, Joseph A.

Article Type: Research Article

Abstract: Although osteoarthritis (OA) is not an inevitable consequence of aging, a strong association exists between age and increasing incidence of OA. We hypothesized that this association is due to in vivo articular cartilage chondrocyte senescence which causes an age‐related decline in the ability of the cells to maintain articular cartilage, that is, increasing age increases the risk of OA because chondrocytes lose their ability to replace their extracellular matrix. To test this hypothesis, we measured senescence markers in human articular cartilage chondrocytes from 27 donors ranging in age from one to 87 years. The markers included expression of the senescence‐associated …enzyme β‐galactosidase, mitotic activity measured by 3 H‐thymidine incorporation, and telomere length. β‐galactosidase expression increased with age (r=0.84, p=0.0001) while mitotic activity and mean telomere length declined (r=−0.774, p=0.001 and r=−0.71, p=0.0004, respectively). Decreasing telomere length was strongly correlated with increasing expression of β‐galactosidase and decreasing mitotic activity. These findings help explain the previously reported age related declines in chondrocyte synthetic activity and responsiveness to anabolic growth factors and indicate that in vivo articular cartilage chondrocyte senescence is responsible, at least in part, for the age related increased incidence of OA. The data also imply that people vary in their risk of developing OA because of differences in onset of chondrocyte senescence; and, the success of chondrocyte transplantation procedures performed to restore damaged articular surfaces in older patients could be limited by the inability of older chondrocytes to form new cartilage. New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 145-152, 2002

Authors: Tonon, Rossana | D'Andrea, Paola

Article Type: Research Article

Abstract: Cell‐to‐cell interactions and gap junctions‐dependent communication are crucially involved in chondrogenic differentiation, while in adult articular cartilage direct intercellular communication occurs mainly among chondrocytes facing the outer cartilage layer. Chondrocytes extracted from adult articular cartilage and grown in primary culture express connexin 43 and form functional gap junctions capable of sustaining the propagation of intercellular Ca2+ waves. Degradation of articular cartilage is a characteristic feature of arthritic diseases and is associated to increased levels of interleukin‐1 (IL‐1) in the synovial fluid. We have examined the effects of IL‐1 on gap junctional communication in cultured rabbit articular chondrocytes. Incubation with …IL‐1 potentiated the transmission of intercellular Ca2+ waves and the intercellular transfer of Lucifer yellow. The stimulatory effect was accompanied by a dose‐dependent increase in the expression of connexin 43 and by an enhanced connexin 43 immunostaining at sites of cell‐to‐cell contact. IL‐1 stimulation induced a dose‐dependent increase of cytosolic Ca2+ and activates protein tyrosine phosphorylation. IL‐1‐dependent up‐regulation of connexin 43 could be prevented by intracellular Ca2+ chelation, but not by inhibitors of protein tyrosine kinases, suggesting a crucial role of cytosolic Ca2+ in regulating the expression of connexin 43. IL‐1 is one of the most potent cytokines that promotes cartilage catabolism: its modulation of intercellular communication represents a novel mechanism by which proinflammatory mediators regulate the activity of cartilage cells. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 153-160, 2002

Authors: Töyräs, J. | Nieminen, H.J. | Laasanen, M.S. | Nieminen, M.T. | Korhonen, R.K. | Rieppo, J. | Hirvonen, J. | Helminen, H.J. | Jurvelin, J.S.

Article Type: Research Article

Abstract: Osteoarthrosis is the most important joint disease that threatens health of the musculoskeletal system of elderly people. Today, there is a need for sensitive, quantitative diagnostic methods for successful and early diagnosis of the disorder. In the present study, we aimed at evaluating the applicability of ultrasound for quantitative assessment of cartilage structure and properties. Bovine articular cartilage was investigated both in vitro and in situ using high frequency ultrasound. Cartilage samples were also tested mechanically in vitro to reveal relationships between acoustic and mechanical parameters of the tissue. The collagen organization and proteoglycan content of cartilage samples were mapped, …using quantitative polarized light microscopy and digital densitometry, respectively, to reveal their effect on the acoustic properties of tissue. The high frequency pulse‐echo ultrasound (20–30 MHz) technique proved to be sensitive in detecting the degeneration of the superficial collagen‐rich cartilage zone. In addition, ultrasound was found to be a potential tool for measuring cartilage thickness. When the results from biomechanical indentation measurements and ultrasound measurements of normal and enzymatically degraded articular cartilage were combined, collagen or proteoglycan degradation in the tissue could be sensitively and specifically differentiated from each other. To conclude, high frequency ultrasound is a useful tool for evaluation of the quality of superficial articular cartilage as well as for the measurement of cartilage thickness. Therefore, ultrasound appears to be a valuable supplement to the mechanical measurements of articular cartilage stiffness. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 161-169, 2002

Authors: Colville‐Nash, Paul R. | Willoughby, Derek A.

Article Type: Research Article

Abstract: It is widely accepted that whilst exhibiting clinically useful anti‐inflammatory and analgesic activity, the application of non‐steroidal anti‐inflammatory drugs (NSAIDs) does not affect the underlying pathogenesis of articular diseases such as rheumatoid arthritis. The demonstration of a role for COX‐2 in the resolution of inflammation may partly underly the lack of disease modifying activity seen with NSAIDs in long term use in these inflammatory joint diseases. This has led to the suggestion that the anti‐arthritic efficacy of these agents may be improved by altering prescribing practice such that they are not given during periods of disease remission, which may be …difficult to achieve in the clinic. Alternatively, they may benefit from concomitant administration of chondroprotective agents, such as diacetylrhein, which may protect against the deleterious effects of traditional NSAIDs on cartilage degradation and, further, inhibit additional pathways such as cytokine elaboration which are important in joint destruction. Show more

Citation: Biorheology, vol. 39, no. 1-2, pp. 171-179, 2002