Suppression of Genes Related to Hypertrophy and Osteogenesis in Committed Human Mesenchymal Stem Cells Cultured on Novel Nitrogen-Rich Plasma Polymer Coatings

Mwale, Fackson; Girard‐Lauriault, Pierre‐Luc; Wang, Hong; Lerouge, Sophie; Antoniou, John; Wertheimer, M. R.

doi:10.1089/ten.2006.12.2639

Cited by 84 publications

(92 citation statements)

References 30 publications

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“…COL10A1 is a marker gene for hypertrophic chondrocyte differentiation [24,25]. At day 6, the COL10A1 message was increased significantly with Npx supplementation in the culture medium ( P = 0.007), while no significant difference was found at days 3 and 12 (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…At day 6, the COL10A1 message was increased significantly with Npx supplementation in the culture medium ( P = 0.007), while no significant difference was found at days 3 and 12 (Figure 1A). Alkaline phosphatase ( ALP ), osteopontin ( OPN ), osteocalcin ( OC ) and COL1A1 are important genes that define the osteogenesis of MSCs [24-26]. To test the effect of Npx on osteogenesis of MSCs, the expression of these genes was examined after MSCs were cultured in osteogenic differentiation medium with or without Npx for 3, 6 and 12 days.…”

Section: Resultsmentioning

confidence: 99%

“…Osteogenesis occurs through an endochondral process involving cellular hypertrophy and mineralization in a manner analogous to the growth plate. Type X collagen is a marker of hypertrophy, whereas ALP, OC, OPN and COL1A1 are bone matrix proteins synthesized by osteoblasts [24-26]. Mineralization is a functional endpoint reflecting advanced osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules

et al. 2014

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IntroductionWe previously showed that type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification), is constitutively expressed by mesenchymal stem cells (MSCs) from osteoarthritis patients and this may be related to Naproxen (Npx), a nonsteroidal anti-inflammatory drug used for therapy. Hedgehog (HH) signaling plays an important role during the development of bone. We tested the hypothesis that Npx affected osteogenic differentiation of human MSCs through the expression of Indian hedgehog (IHH), Patched-1 (PTC1) and GLI family members GLI1, GLI2, GLI3 in vitro.MethodsMSCs were cultured in osteogenic differentiation medium without (control) or with 0.5 μM Npx. The expression of collagen type X, alpha 1 (COL10A1), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OC), collagen type I, alpha 1 (COL1A1) was analyzed with real-time reverse transcription (RT) PCR, and the ALP activity was measured. The osteogenesis of MSCs was monitored by mineral staining and quantification with alizarin red S. To examine whether Npx affects osteogenic differentiation through HH signaling, the effect of Npx on the expression of IHH, GLI1, GLI2, GLI3 and PTC1 was analyzed with real-time RT PCR. The effect of cyclopamine (Cpn), a HH signaling inhibitor, on the expression of COL10A1, ALP, OC and COL1A1 was also determined.ResultsWhen MSCs were cultured in osteogenic differentiation medium, Npx supplementation led to a significant decrease in ALP gene expression as well as its activity, and had a tendency to decrease mineral deposition. It also decreased the expression of COL1A1 significantly. In contrast, the gene expression of COL10A1 and OPN were upregulated significantly by Npx. No significant effect was found on OC expression. The expression of IHH, PTC1, GLI1, and GLI2 was increased by Npx, while no significant difference was observed on GLI3 expression. Cpn reversed the effect of Npx on the expression of COL10A1, ALP, OPN and COL1A1.ConclusionsThese results indicate that Npx can affect gene expression during osteogenic differentiation of MSCs, and downregulate mineral deposition in the extracellular matrix through IHH signaling. Therefore, Npx could affect MSC-mediated repair of subchondral bone in OA patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules

et al. 2014

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“…Several studies have found that TGF-β stimulates chondrogenic gene and protein expression in MSC differentiation [3][4][5]. TGF-β could induce chondrogenic differentiation of MSC [1], but several disadvantages are associated with its use such as the formation of an unfavourable hypertrophic cartilage phenotype which followed by endochondral ossification instead of permanent chondrogenesis [6][7][8][9]. Mechanical loading induces chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) as effective as TGF-β [10,11] and it might enhance TGF-β receptors and also influences on TGF-β intracellular pathway molecules [12].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound Effect on Gene Expression of Sex Determining Region Y-box 9 (SOX9) and Transforming Growth Factor β Isoforms in Adipose Stem Cells

Shafaei

Baghernezhad

2016

Zahedan J Res Med Sci

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“…We recently showed that a novel atmospheric-pressure plasma-polymerized thin film material, named " nitrogen-rich plasma-polymerized ethylene " (PPE:N), is able to inhibit hypertrophy as well as osteogenesis in committed human MSCs from OA patients [6]. In contrast, neither aggrecan nor type I collagen expression were significantly affected.…”

Section: Introductionmentioning

confidence: 99%

Effect of nitrogen-rich cell culture surfaces on type X collagen expression by bovine growth plate chondrocytes

et al. 2011

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BackgroundRecent evidence indicates that osteoarthritis (OA) may be a systemic disease since mesenchymal stem cells (MSCs) from OA patients express type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification). We recently showed that the expression of type X collagen was suppressed when MSCs from OA patients were cultured on nitrogen (N)-rich plasma polymer layers, which we call "PPE:N" (N-doped plasma-polymerized ethylene, containing up to 36 atomic percentage (at.% ) of N.MethodsIn the present study, we examined the expression of type X collagen in fetal bovine growth plate chondrocytes (containing hypertrophic chondrocytes) cultured on PPE:N. We also studied the effect of PPE:N on the expression of matrix molecules such as type II collagen and aggrecan, as well as on proteases (matrix metalloproteinase-13 (MMP-13) and molecules implicated in cell division (cyclin B2). Two other culture surfaces, "hydrophilic" polystyrene (PS, regular culture dishes) and nitrogen-containing cation polystyrene (Primaria®), were also investigated for comparison.ResultsResults showed that type X collagen mRNA levels were suppressed when cultured for 4 days on PPE:N, suggesting that type X collagen is regulated similarly in hypertrophic chondrocytes and in human MSCs from OA patients. However, the levels of type X collagen mRNA almost returned to control value after 20 days in culture on these surfaces. Culture on the various surfaces had no significant effects on type II collagen, aggrecan, MMP-13, and cyclin B2 mRNA levels.ConclusionHypertrophy is diminished by culturing growth plate chondrocytes on nitrogen-rich surfaces, a mechanism that is beneficial for MSC chondrogenesis. Furthermore, one major advantage of such "intelligent surfaces" over recombinant growth factors for tissue engineering and cartilage repair is potentially large cost-saving.

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Suppression of Genes Related to Hypertrophy and Osteogenesis in Committed Human Mesenchymal Stem Cells Cultured on Novel Nitrogen-Rich Plasma Polymer Coatings

Cited by 84 publications

References 30 publications

Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules

Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules

Ultrasound Effect on Gene Expression of Sex Determining Region Y-box 9 (SOX9) and Transforming Growth Factor β Isoforms in Adipose Stem Cells

Effect of nitrogen-rich cell culture surfaces on type X collagen expression by bovine growth plate chondrocytes

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