Subtractive gene expression profiling of articular cartilage and mesenchymal stem cells: serpins as cartilage-relevant differentiation markers

Boeuf, Stéphane; Steck, Eric; Pelttari, Karoliina; Hennig, T.; Buneß, Andreas; Benz, Karin; Witte, Daniela; Sültmann, Holger; Poustka, Annemarie; Richter, Wiltrud

doi:10.1016/j.joca.2007.05.008

Cited by 52 publications

(48 citation statements)

References 35 publications

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“…COL14A1, known to be densely packed on mature collagen such as type I collagen structures, was also found to be induced (Schuppan et al, 1990). High serpin peptidase inhibitor, clade F1 (SERPINF1) gene expression levels are known from cultured MSC but not from native cartilage, which further indicates dedifferentiation (Boeuf et al, 2007). Additionally, a continuously increased expression of genes related to proliferation (GAS6, SERPINF1, VEGFB and VEGFC) and apoptotic events (APOE, DAPK1 and DRAM) was observed further suggesting a progressed dedifferentiation and degeneration in six week cultures compared to three week cultures or uncultured cells.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of primary human articular chondrocytes in high-density micromasses reveals patterns of recovery, maintenance, re- and dedifferentiation

Dehne

Schenk

Perka

et al. 2010

Gene

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling of primary human articular chondrocytes in high-density micromasses reveals patterns of recovery, maintenance, re- and dedifferentiation

Dehne

Schenk

Perka

et al. 2010

Gene

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“…Differences between MSC- and chondrocyte-based engineered constructs have been investigated on the molecular, microscopic tissue, and macroscopic tissue level (Boeuf et al, 2008; Farrell et al, 2012; Huang et al, 2010c). Multiple studies have noted that MSC-based constructs increase in content and properties for a period of time, before reaching a plateau in cartilage-like matrix content and macroscopic (whole tissue level) equilibrium mechanical properties (Huang et al, 2010a; Mauck et al, 2006; Vinardell et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Functional properties of bone marrow-derived MSC-based engineered cartilage are unstable with very long-term in vitro culture

Farrell¹,

Fisher²,

Huang³

et al. 2014

Journal of Biomechanics

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The success of stem cell-based cartilage repair requires that the regenerate tissue reach a stable state. To investigate the long term stability of tissue engineered cartilage constructs, we assessed the development of compressive mechanical properties of chondrocyte and mesenchymal stem cell (MSC)-laden three dimensional agarose constructs cultured in a well defined chondrogenic in vitro environment through 112 days. Consistent with previous reports, in the presence of TGF-β, chondrocytes outperformed MSCs through day 56, under both free swelling and dynamic culture conditions, with MSC-laden constructs reaching a plateau in mechanical properties between days 28 and 56. Extending cultures through day 112 revealed that MSCs did not simply experience a lag in chondrogenesis, but rather that construct mechanical properties never matched those of chondrocyte-laden constructs. After 56 days, MSC-laden constructs underwent a marked reversal in their growth trajectory, with significant declines in glycosaminoglycan content and mechanical properties. Quantification of viability showed marked differences in cell health between chondrocytes and MSCs throughout the culture period, with MSC-laden construct cell viability falling to very low levels at these extended time points. These results were not dependent on the material environment, as similar findings were observed in a photocrosslinkable hyaluronic acid (HA) hydrogel system that is highly supportive of MSC chondrogenesis. These data suggest that, even within a controlled in vitro environment that is conducive to chondrogenesis, there may be an innate instability in the MSC phenotype that is independent of scaffold composition, and may ultimately limit their application in functional cartilage repair.

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“…Similarly, manual identification of DEGs demonstrated that exercise-induced biosynthesis of ECM structural proteins, growth factors ( Fgf2 , Fgf13 , and Fgf14 ), and signaling molecules, while inhibiting expression of non-cartilaginous DEGs ( Col9a2, Col9a3, Col1a2, and Ctsk ) 29, 31, 34–38 . In fact, exercise negatively regulated expression of enzymes involved in ECM degradation, while upregulating expression of inhibitors of proteases involved in ECM degradation ( TIMP14, Serpina 1, Serpina 3a, and Mug1 & 2 ) 39 . Thus our findings support the earlier observations that exercise strengthens healthy joints, and further provide molecular evidence that exercise activates metabolic pathways critical for maintaining ECM production, limiting cartilage destruction and maintaining the cartilage-specific tissue phenotype to protect its integrity and structural strength 1, 40–42 .…”

Section: Discussionmentioning

confidence: 99%

Exercise-driven metabolic pathways in healthy cartilage

Blazek

Nam

Gupta

et al. 2016

Osteoarthritis and Cartilage

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SUMMARY Objective Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for its potential benefits. Methods Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise. Results Microarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of Functional Annotation Clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage. Conclusions Overall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage.

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Subtractive gene expression profiling of articular cartilage and mesenchymal stem cells: serpins as cartilage-relevant differentiation markers

Cited by 52 publications

References 35 publications

Gene expression profiling of primary human articular chondrocytes in high-density micromasses reveals patterns of recovery, maintenance, re- and dedifferentiation

Gene expression profiling of primary human articular chondrocytes in high-density micromasses reveals patterns of recovery, maintenance, re- and dedifferentiation

Functional properties of bone marrow-derived MSC-based engineered cartilage are unstable with very long-term in vitro culture

Exercise-driven metabolic pathways in healthy cartilage

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