Discrimination of meniscal cell phenotypes using gene expression profiles

Son, Min-Sun; Levenston, Marc E.

doi:10.22203/ecm.v023a15

Cited by 21 publications

(34 citation statements)

References 58 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidence suggests that the meniscus may have a more biologically active role in the complicated whole joint pathology of osteoarthritis 11, 15, 18, 28, 29 . Many of these studies use animal meniscus specimens and are limited in their translation to human osteoarthritis pathogenesis 30 . Our data using cultured human meniscal tissue expands upon previous gene expression reports 10, 11, 18 using RNA isolated from normal and osteoarthritic human meniscus and further support a role for meniscus involvement in osteoarthritis pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…We opted to examine the entire cell population in the meniscus to elucidate differences between the normal meniscus and the osteoarthritis disease state. Additional studies have examined the differences in meniscus cell type 18, 30 , so we believe our characterization of normal and osteoarthritis human meniscus may add to a better understanding of osteoarthritis pathogenesis following meniscal injury.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

Stone

Loeser

Vanderman

et al. 2014

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

Objective Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development. Design Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide. Results Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production. Conclusions Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

Stone

Loeser

Vanderman

et al. 2014

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

show abstract

“…Human menisci are composed of different cell populations that are able to respond differently to the stimuli belonging to the matrix (Verdonk et al ., ; Son and Levenston, ). According to the complex nature of the meniscal tissue, two cell populations have mainly been used in studies on meniscal healing: mesenchymal stem/stromal cells (MSCs) and chondrocytes.…”

Section: Meniscal Repairmentioning

confidence: 98%

Animal models for meniscus repair and regeneration

Deponti

Giancamillo

Scotti

et al. 2013

J Tissue Eng Regen Med

View full text Add to dashboard Cite

The meniscus plays an important role in knee function and mechanics. Meniscal lesions, however, are common phenomena and this tissue is not able to achieve spontaneous successful repair, particularly in the inner avascular zone. Several animal models have been studied and proposed for testing different reparative approaches, as well as for studying regenerative methods aiming to restore the original shape and function of this structure. This review summarizes the gross anatomy, function, ultrastructure and biochemical composition of the knee meniscus in several animal models in comparison with the human meniscus. The relevance of the models is discussed from the point of view of basic research as well as of clinical translation for meniscal repair, substitution and regeneration. Finally, the advantages and disadvantages of each model for various research directions are critically discussed.

show abstract

“…The cells become progressively more fibroblast‐like and exhibit more stellate morphologies towards the outer, tensile region, where collagen I is highly expressed (Hellio Le Graverand et al ., ; Upton et al ., ). We recently found that a combination of three gene expression ratios, Collagen I/Collagen II, Collagen VI/Collagen II and ADAMTS‐5/Collagen II, could be used to accurately discriminate among articular chondrocytes and fibrochondrocytes from different meniscal regions, with continuous variations in all three ratios from inner to outer regions (Son and Levenston, ).…”

Section: Introductionmentioning

confidence: 99%

Quantitative tracking of passage and 3D culture effects on chondrocyte and fibrochondrocyte gene expression

Son

Levenston

2015

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Success in cartilage and fibrocartilage tissue engineering relies heavily on using an appropriate cell source. Many different cell sources have been identified, including primary and stem cells, along with experimental strategies to obtain the required number of cells or to induce chondrogenesis. However, no definitive method exists to quantitatively evaluate the similarity of the resulting cell phenotypes to those of the native cells between candidate strategies. In this study, we develop an integrative approach to enable such evaluations by deriving, from gene expression profiles, two quantitative metrics representing the nearest location within the range of native cell phenotypes and the deviation from it. As an example application to evaluating potential cell sources for cartilage or meniscus tissue engineering, we examine phenotypic changes of juvenile and adult articular chondrocytes and fibrochondrocytes across multiple passages and subsequent 3D culture. A substantial change was observed in cell phenotype due to the isolation process itself, followed by a clear progression toward the outer meniscal cell phenotype with passage. The new metrics also indicated that 3D culture moderately reduced the passage-induced deviation from the native meniscal phenotypes for juvenile chondrocytes and adult fibrochondrocytes, which was not obvious through examination of individual gene expressions. However, brief 3D culture alone did not move any of the cells towards an inner meniscal phenotype, the most relevant target for meniscal tissue engineering. This integrative approach of examining and combining multiple gene expressions can be used to evaluate various other tissue-engineering strategies to direct cells toward the desired phenotype. Copyright © 2015 John Wiley & Sons, Ltd.

show abstract

Discrimination of meniscal cell phenotypes using gene expression profiles

Cited by 21 publications

References 58 publications

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

Animal models for meniscus repair and regeneration

Quantitative tracking of passage and 3D culture effects on chondrocyte and fibrochondrocyte gene expression

Contact Info

Product

Resources

About