A Tale of Two Loads: Modulation of IL-1 Induced Inflammatory Responses of Meniscal Cells in Two Models of Dynamic Physiologic Loading (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.
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.
Scientific Data, 2022
Osteoarthritis (OA) primarily affects mechanical load-bearing joints, with the knee being the most common. The prevalence, burden and severity of knee osteoarthritis (KOA) are disproportionately higher in females, but hormonal differences alone do not explain the disproportionate incidence of KOA in females. Mechanical unloading by spaceflight microgravity has been implicated in OA development in cartilaginous tissues. However, the mechanisms and sex-dependent differences in OA-like development are not well explored. In this study, engineered meniscus constructs were generated from healthy human meniscus fibrochondrocytes (MFC) seeded onto type I collagen scaffolds and cultured under normal gravity and simulated microgravity conditions. We report the whole-genome sequences of constructs from 4 female and 4 male donors, along with the evaluation of their phenotypic characteristics. The collected data could be used as valuable resources to further explore the mechanism of KOA development in response to mechanical unloading, and to investigate the molecular basis of the observed sex differences in KOA.
Cell sources of inflammatory mediators present in bone marrow areas inside the meniscus
PLOS ONE, 2019
To demonstrate the production of inflammatory mediators by cells located in bone marrow spaces inside rodent menisci. Methods Mice subjected to transection of the medial collateral and anterior cruciate ligaments and meniscotomy (osteoarthritis model) or to a sham procedure, as well as non-operated (naive) mice and rats, had knee joints excised. Tissues were stained with hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP). CD68 + cells, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, and tumor necrosis factor (TNF) expression were detected using immunohistochemistry. Results Lamellar ossified areas, bone-entrapped osteocytes and bone marrow spaces were found inside menisci of one week up to 6 months-old naïve mice, regardless of gender. Menisci from naive rats also showed the same pattern with bone marrow areas. CD68 + cells were identified in bone marrow areas inside the meniscus of mice. TRAP + osteoclasts, and hematogenous precursors expressing IL-1β, TNF, and iNOS were identified inside bone marrow areas in meniscal samples from both naïve and sham operated mice. Quantitative immunoexpression of IL-1 β, TNF and iNOS was more intense, P = 0.0194, 0.0293, 0.0124, respectively, in mouse knees from mice sacrificed 49 days after being subjected to an osteoarthritis (OA) model as compared to sham operated animals.
Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression
Journal of Tissue Engineering
This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human MFCs on a collagen scaffold were stimulated to form fibrocartilage over 6 weeks under normoxic (NRX, 20% O2) conditions with supplemented TGF-β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O2) and then 5 min of dynamic compression (DC) between 30 and 40% strain. Delayed HYP induced an anabolic and anti-catabolic expression profile for hyaline cartilage matrix markers, while DC induced an inflammatory matrix remodeling response along with upregulation of both SOX9 and COL1A1. There were 41 genes regulated by both HYP and DC. Overall, the combined treatment supported a unique gene expression profile favouring the hyaline ca...
The effect of dynamic mechanical compression on nitric oxide production in the meniscus
Osteoarthritis and Cartilage, 2001
Objective: The menisci play an important role in the biomechanics of the knee, and loss of meniscal function has been associated with progressive degenerative changes of the joint in rheumatoid arthritis as well as in osteoarthritis. However, little is known about the underlying mechanisms that link meniscal injury or degeneration to arthritis. Meniscal fibrochondrocytes respond to environmental mediators such as growth factors and cytokines, but the influence of mechanical stress on their metabolic activity is not well understood. Nitric oxide (NO) is believed to play a role in mechanical signal transduction, and there is also significant evidence of its role in cartilage and meniscus degeneration. The goal of this study was to determine if meniscal fibrochondrocytes respond to mechanical stress by increasing NO production in vitro.
Arthritis & Rheumatism, 2013
Objective-Meniscus tears are associated with a heightened risk for osteoarthritis. We aimed to advance our understanding of the metabolic state of human injured meniscus at the time of arthroscopic partial meniscectomy through transcriptome-wide analysis of gene expression in relation to patient age and degree of cartilage chondrosis. Methods-The degree of chondrosis of knee cartilage was recorded at the time of meniscectomy in symptomatic patients without radiographic osteoarthritis. RNA preparations from resected menisci (N=12) were subjected to transcriptome-wide microarray and QuantiGene Plex analyses. The relative changes in gene expression variation with age and chondrosis were analyzed and integrated biological processes were investigated computationally. Results-We identified a set of genes in torn meniscus that were differentially expressed with age and chondrosis. There were 866 genes differentially regulated (≥1.5-fold; P<0.05) with age and 49 with chondrosis. In older patients, genes associated with cartilage and skeletal development and extracellular matrix synthesis were repressed while those involved in immune response, inflammation, cell cycle, and cellular proliferation were stimulated. With chondrosis, genes representing cell catabolism (cAMP catabolic process) and tissue and endothelial cell development were repressed and those involved in T cell differentiation and apoptosis were elevated. Conclusion-Differences in age-related gene expression suggest that in older adults, meniscal cells might de-differentiate and initiate a proliferative phenotype. Conversely, meniscal cells in
Journal of experimental orthopaedics, 2016
Meniscal injuries are a risk factor for osteoarthritis (OA). While a mechanical pathway between meniscal injury and OA has been described, the biological effects of inflammation on this pathway have yet to be clarified. The aim of our study was to compare levels of specific inflammatory mediators, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nerve growth factor (NGF), in injured and uninjured meniscal tissue and related knee joint synovium. Tissue samples were obtained from 19 patients, 31.1 ± 13.6 years old, who underwent arthroscopic partial meniscectomy. For analysis, tissue samples were categorized into the following groups: injured meniscal site (IM), non-injured meniscal site (NIM), synovium 'nearest' the lesion (NS), and synovium from the opposite knee compartment, 'farthest' synovium (FS). Levels of inflammatory mediators were determined using enzyme-linked immunosorbent assay and between-group differences (IM and NIM; NS and FS) were evalua...
Traumatic and Degenerative Meniscus Tears Have Different Gene Expression Signatures
The American journal of sports medicine, 2016
Meniscus tears are classified as traumatic or degenerative based on the tear pattern. There is little evidence demonstrating biological differences between the 2 tear types. Gene expression signatures in the injured meniscus are different between traumatic (vertical) and degenerative (complex, horizontal, or flap) tears. Controlled laboratory study. Samples of the torn meniscus from the white-white zone were removed at the time of clinically indicated partial meniscectomy from 48 patients (37 with degenerative tears and 11 with traumatic tears). mRNA expression in the injured menisci was measured by quantitative real-time polymerase chain reaction for selected molecular markers of osteoarthritis, inflammation, and cartilage homeostasis (eg, cytokines/chemokines, aggrecanases/metalloproteinases, transcription factors, cartilage matrix genes, and adipokines). The tear pattern (traumatic or degenerative) and location (medial or lateral) were recorded for each patient. Gene expression d...