The role of TGFβs and Sox9 during limb chondrogenesis

Kawakami, Yasuhiko; Rodríguez-León, Joaquín; Belmonte, Juan Carlos Izpisúa

doi:10.1016/j.ceb.2006.10.007

Cited by 148 publications

(116 citation statements)

References 42 publications

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“…Several chondrogenic genes such as Sox9 and Col2a1 were not changed on the molecular level. 24) However, curcumin inhibited chondrocyte hypertrophy of MSCs. The expression of specific genes related to chondrocyte hypertrophy including Runx2, Mmp13 and Col10a1 were inhibited by curcumin.…”

Section: Discussionmentioning

confidence: 99%

Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways

Cao

Dou

Dong

2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, it is very important to find out a suitable way to maintain the phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving from turmeric was reported with anti-inflammatory and antitumor pharmacological effects. However, the role of curcumin in metabolism of chondrocytes, especially in the chondrocyte hypertrophy remains unclear. Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering as seed cells. So we investigated the effect of curcumin on chondrogenesis and chondrocyte hypertrophy in MSCs through examination of cell viability, glycosaminoglycan synthesis and specific gene expression. We found curcumin had no effect on expression of chondrogenic markers including Sox9 and Col2a1 while hypertrophic markers including Runx2 and Col10a1 were down-regulated. Further exploration showed that curcumin inhibited chondrocyte hypertrophy through Indian hedgehog homolog (IHH) and Notch signalings. Our results indicated curcumin was a potential agent in modulating cartilage homeostasis and maintaining chondrocyte phenotype.Key words curcumin; mesenchymal stem cell; chondrocyte hypertrophy; Indian hedgehog homolog; neurogenic locus notch homolog Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and disability.1) Seventy percent of the population older than 65 years is suffering from varying degrees of OA.2)The pathogenesis of cartilage injury caused by OA is the disruption of the homeostasis between catabolism and anabolism of extracellular matrix.3) However, limited by the intrinsic regeneration capacity of cartilage tissue, repairing damaged articular cartilage currently is a significant challenge. 4,5) With the advances in materials science, cell biology, biomechanics, using tissue engineering technology to construct cartilage provides a novel method for repairing damaged cartilage.6) Mesenchymal stem cells (MSCs) have potential of differentiation into chondrocytes and have got the priority in the seed cells choosing list because of their traits in rich resources, easy to get and low immunogenicity. 7,8) However, the regenerated tissue-engineered cartilage usually is fibrous cartilage rather than hyaline cartilage.9) The chondrocytes in fibrous cartilage proceed in hypertrophic differentiation and secret Col10a1 and matrix metalloproteinase 13 (Mmp13).10) Therefore, suppressing chondrocyte hypertrophy is the key issue to build a stable hyaline cartilage.Curcumin is effective substance of turmeric and possesses various pharmacological effects, including antioxidant, anti-bacterial, anti-tumor and anti-inflammatory.11-13) A recent study has reported that curcumin may be a potential therapeutic candidate for Helicobacter pylori associated diseas...

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Section: Discussionmentioning

confidence: 99%

Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways

Cao

Dou

Dong

2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…In recent report, Sox9 expression during chondrogenesis might be under direct control of TGF-β /BMP activity, and that factors downstream of TGF-β /BMP pathways, such as Smads and TAK1 (TGF-βactivated kinase), control chondrogenesis-specific enhancers of the Sox9 gene 3) . In this study, TGF-β 1 increased protein level as well as mRNA expression of Sox9 very highly, and moreover the mRNA level of versican that is a large aggrecating proteoglycan mainly distributed in nucleus pulposus was also increased by TGF-β 1 treatment.…”

Section: Discussionmentioning

confidence: 99%

The Relation Between Sox9, TGF-β1, and Proteoglycan in Human Intervertebral Disc Cells

Lee

Kong

Song

et al. 2008

J Korean Neurosurg Soc

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“…Aggregating cells by pelleting or plating them at a high density, followed by growth in chondrogenic culture medium that contains members of the transforming growth factor beta (TGF-b) family and other growth factors, results in the completion of the condensation step. In addition, this process activates those changes in gene expression that are required for differentiation (Chimal-Monroy and Diaz de Leon, 1999;Kawakami et al, 2006). In particular, the expression of type II collagen and aggrecan is upregulated at this point, which promotes the deposition of a cartilage-specific ECM.…”

Section: Fibronectin and Chondrogenesis 3705mentioning

confidence: 99%

Fibronectin and stem cell differentiation – lessons from chondrogenesis

Singh

Schwarzbauer

2012

Journal of Cell Science

162

145

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SummaryThe extracellular matrix (ECM) is an intricate network of proteins that surrounds cells and has a central role in establishing an environment that is conducive to tissue-specific cell functions. In the case of stem cells, this environment is the stem cell niche, where ECM signals participate in cell fate decisions. In this Commentary, we describe how changes in ECM composition and mechanical properties can affect cell shape and stem cell differentiation. Using chondrogenic differentiation as a model, we examine the changes in the ECM that occur before and during mesenchymal stem cell differentiation. In particular, we focus on the main ECM protein fibronectin, its temporal expression pattern during chondrogenic differentiation, its potential effects on functions of differentiating chondrocytes, and how its interactions with other ECM components might affect cartilage development. Finally, we discuss data that support the possibility that the fibronectin matrix has an instructive role in directing cells through the condensation, proliferation and/or differentiation stages of cartilage formation.

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The role of TGFβs and Sox9 during limb chondrogenesis

Cited by 148 publications

References 42 publications

Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways

Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways

The Relation Between Sox9, TGF-β1, and Proteoglycan in Human Intervertebral Disc Cells

Fibronectin and stem cell differentiation – lessons from chondrogenesis

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