The effect of dynamic mechanical compression on nitric oxide production in the meniscus (original) (raw)
Related papers
Osteoarthritis and Cartilage, 2004
Cells of the knee meniscus respond to changes in their biochemical and biomechanical environments with alterations in the biosynthesis of matrix constituents and inflammatory mediators. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that is involved in the pathogenesis of both osteoarthritis and rheumatoid arthritis, but its influence on meniscal physiology or mechanobiology is not fully understood. The objectives of this study were to examine the hypothesis that cyclic mechanical strain of meniscal cells modulates the biosynthesis of matrix macromolecules and pro-inflammatory mediators, and to determine if this response is altered by TNF-α.Cells were isolated from the inner two-thirds of porcine medial menisci and subjected to biaxial tensile strain of 5–15% at a frequency of 0.5 Hz. The synthesis of proteoglycan, protein, nitric oxide (NO), and prostaglandin E2 were determined.Cyclic tensile strain increased the production of nitric oxide through the upregulation of nitric oxide synthase 2 (NOS2) and also increased synthesis rates of prostaglandin E2, proteoglycan, and total protein in a manner that depended on strain magnitude. TNF-α increased the production of NO and total protein, but inhibited proteoglycan synthesis rates. TNF-α prevented the mechanical stimulation of proteoglycan synthesis, and this effect was not dependent on NOS2.These findings indicate that pro-inflammatory cytokines can modulate the responses of meniscal cells to mechanical signals, suggesting that both biomechanical and inflammatory factors could contribute to the progression of joint disease as a consequence of altered loading of the meniscus.
Biochemical and Biophysical Research Communications, 2007
Injury or loss of the knee meniscus is associated with altered joint stresses that lead to progressive joint degeneration. The goal of this study was to determine if dynamic mechanical compression influences the production of inflammatory mediators by meniscal cells. Dynamic compression increased prostaglandin E2 (PGE 2 ) and nitric oxide (NO) production over a range of stress magnitudes (0.0125-0.5 MPa) in a manner that depended on stress magnitude and zone of tissue origin. Inner zone explants showed greater increases in PGE 2 and NO production as compared to outer zone explants. Meniscal tissue expressed NOS2 and NOS3 protein, but not NOS1. Mechanically-induced NO production was blocked by NOS inhibitors, and the non-selective NOS inhibitor L-NMMA augmented PGE 2 production in the outer zone only. These findings suggest that the meniscus may serve as an intra-articular source of pro-inflammatory mediators, and that alterations in the magnitude or distribution of joint loading could significantly influence the production of these mediators in vivo.
Nitric Oxide Synthase and Cyclooxygenase Interactions in Cartilage and Meniscus
Rheumatoid arthritis and osteoarthritis are painful and debilitating diseases with complex pathophysiology. There is growing evidence that pro-inflammatory cytokines (e.g., interleukin-1 and tumor necrosis factor alpha) and mediators (e.g., prostaglandins, leukotrienes, and nitric oxide) play critical roles in the development and perpetuation of tissue inflammation and damage in joint tissues such as articular cartilage and meniscus. While earlier studies have generally focused on cells of the synovium (especially macrophages), there is increasing evidence that chondrocytes and meniscal cells actively contribute to inflammatory processes. In particular, it is now apparent that mechanical forces engendered by joint loading are transduced to biological signals at the cellular level and that these signals modulate gene expression and biochemical processes. Here we give an overview of the interplay of cytokines and mechanical stress in the production of cyclooxygenases and prostaglandins; lipoxygenases and leukotrienes; and nitric oxide synthases and nitric oxide in arthritis, with particular focus on the interactions of these pathways in articular cartilage and meniscus
Biochemical and Biophysical Research Communications, 1998
In this study, a well-characterized model system utilizing bovine chondrocytes embedded in 3% agarose constructs has been used to investigate the effect of dynamic strain at 0.3, 1, or 3 Hz on NO production. LPS induced a significant increase in nitrite levels, which was reversed by both L-NAME and dexamethasone. Dynamic compressive strain produced a significant reduction in nitrite production. The effect was partially blocked by L-NAME but unaffected by dexamethasone. L-NAME also reversed dynamic compressioninduced stimulation of [ 3 H]-thymidine incorporation. NO appears to be a constituent of mechanotransduction pathways which influence proliferation of bovine chondrocytes seeded within agarose constructs. The inhibitor experiments also infer that alterations in cNOS activity primarily determine the response.
Journal of Orthopaedic Research, 2001
Nitric oxide (NO) production and NO synthase (NOS) expression are increased in osteoarthritis and rheumatoid arthritis, suggesting that NO may play a role in the destruction of articular cartilage. To test the hypothesis that mechanical stress may increase NO production by chondrocytes, we measured the eects of physiological levels of static and intermittent compression on NOS activity, NO production, and NOS antigen expression by porcine articular cartilage explants. Static compression signi®cantly increased NO production at 0.1 MPa stress for 24 h (P < 0:05). Intermittent compression at 0.5 Hz for 6 h followed by 18 h recovery also increased NO production and NOS activity at 1.0 MPa stress (P < 0:05). Intermittent compression at 0.5 Hz for 24 h at a magnitude of 0.1 or 0.5 MPa caused an increase in NO production and NOS activity (P < 0:05). Immunoblot analysis showed stress-induced upregulation of NOS2, but not NOS1 or NOS3. There was no loss in cell viability following any of the loading regimens. Addition of 2 mM 1400 W (a speci®c NOS2 inhibitor) reduced NO production by 51% with no loss of cell viability. These ®ndings indicate that NO production by chondrocytes is in¯uenced by mechanical compression in vitro and suggest that biomechanical factors may in part regulate NO production in vivo. Ó
Differential effects of static and dynamic compression on meniscal cell gene expression
Journal of orthopaedic …, 2003
Cells of the meniscus are exposed to a wide range of time-varying mechanical stimuli that may regulate their metabolic activity in vivo. In this study, the biological response of the meniscus to compressive stimuli was evaluated in vitro, using a well-controlled explant culture system. Gene expression for relevant extracellular matrix proteins was quantified using real-time RT-PCR following a 24 h period of applied static (0.1 MPa compressive stress) or dynamic compression (0.08-0.16 MPa). Static and dynamic compression were found to differentially regulate mRNA levels for specific proteins of the extracellular matrix. Decreased mRNA levels were observed for decorin (-2. I fold-difference) and type I1 collagen (-4.0 fold-difference) following 24 h of dynamic compression. Decorin mRNA levels also decreased following static compression (-4.5 fold-difference), as did mRNA levels for both types I (-3.3 fold-difference) and I1 collagen (-4.0 fold-difference). Following either static or dynamic compression, mRNA levels for aggrecan, biglycan and cytoskeletal proteins were unchanged. It is noteworthy that static compression was associated with a 2.6 fold-increase in mRNA levels for collagenase, or MMP-I, suggesting that the homeostatic balance between collagen biosynthesis and catabolism was altered by the mechanical stimuli. These findings demonstrate that the biosynthetic response of the meniscus to compression is regulated, in part, at the transcriptional level and that transcription of types I and I1 collagen as well as decorin may be regulated by common mechanical stimuli.
BMC musculoskeletal disorders, 2014
Traumatic impaction is known to cause acute cell death and macroscopic damage to cartilage and menisci in vitro. The purpose of this study was to investigate cell viability and macroscopic damage of the medial and lateral menisci using an in situ model of traumatic loading. Furthermore, the release of nitric oxide from meniscus, synovium, cartilage, and subchondral bone was also documented. The left limbs of five rabbits were subjected to tibiofemoral impaction resulting in anterior cruciate ligament (ACL) rupture and meniscal damage. Meniscal tear morphology was assessed immediately after trauma and cell viability of the lateral and medial menisci was assessed 24 hrs post-injury. Nitric oxide (NO) released from joint tissues to the media was assayed at 12 and 24 hrs post injury. ACL and meniscal tearing resulted from the traumatic closed joint impact. A significant decrease in cell viability was observed in the lateral menisci following traumatic impaction compared to the medial me...
Mechanical Stress and Nitric Oxide Influence Leukotriene Production in Cartilage
Biochemical and Biophysical Research Communications, 2001
Nitric oxide (NO) and leukotrienes regulate a variety of processes in joint tissues and are frequently elevated in arthritis. Mechanical stress can induce biochemical and functional changes in cartilage that may influence mediator production. To investigate the relationship between mechanical stress and the production of leukotriene B 4 (LTB 4 ) and NO, explants of porcine articular cartilage were subjected to mechanical compression for 1 h followed by 23 h recovery in the presence or absence of the NOS2 inhibitor 1400W. Dynamic compression significantly increased LTB 4 and LOX protein production in the presence of 1400W. The induced LTB 4 was functional as evidenced by its ability to promote chemotaxis of RBL-2H3 cells expressing the LTB 4 receptor. Increased LOX protein but not LTB 4 occurred in response to compression alone. These findings provide a direct link between mechanical stress and inflammation in cartilage and may have implications in the pathogenesis and treatment of arthritis.
Mechanobiology of the meniscus
The meniscus plays a critical biomechanical role in the knee, providing load support, joint stability, and congruity. Importantly, growing evidence indicates that the mechanobiologic response of meniscal cells plays a critical role in the physiologic, pathologic, and repair responses of the meniscus. Here we review experimental and theoretical studies that have begun to directly measure the biomechanical effects of joint loading on the meniscus under physiologic and pathologic conditions, showing that the menisci are exposed to high contact stresses, resulting in a complex and nonuniform stress-strain environment within the tissue. By combining microscale measurements of the mechanical properties of meniscal cells and their pericellular and extracellular matrix regions, theoretical and experimental models indicate that the cells in the meniscus are exposed to a complex and inhomogeneous environment of stress, strain, fluid pressure, fluid flow, and a variety of physicochemical factors. Studies across a range of culture systems from isolated cells to tissues have revealed that the biological response of meniscal cells is directly influenced by physical factors, such as tension, compression, and hydrostatic pressure. In addition, these studies have provided new insights into the mechanotransduction mechanisms by which physical signals are converted into metabolic or pro/antiinflammatory responses. Taken together, these in vivo and in vitro studies show that mechanical factors play an important role in the health, degeneration, and regeneration of the meniscus. A more thorough understanding of the mechanobiologic responses of the meniscus will hopefully lead to therapeutic approaches to prevent degeneration and enhance repair of the meniscus.
Cellular and molecular meniscal changes in the degenerative knee: a review
Journal of Experimental Orthopaedics
Background: The important role of knee menisci to maintain adequate knee function is frequently impaired since early stages of knee joint degeneration. A better understanding of meniscal impairment may help the orthopaedic surgeon to orient the treatment of the degenerative knee. This review focuses on changes in meniscal cells and matrix when degeneration is in progress. Main body: Differences in the meniscal structure and metabolism have been investigated in the degenerative knee, both in experimental animal models and in surgical specimens. Cell population reduction, extracellular matrix disorganization, disturbances in collagen and non-collagen protein synthesis and/or expression have been found in menisci along with knee degeneration. These changes are considered disease-specific, different from those due to aging. Conclusion: Significant cellular and matrix differences are found in menisci during knee degeneration. These investigations may help to further progress in the understanding of knee degeneration and in the search of more biological treatments.