Functional analysis of fibronectin isoforms in chondrogenesis: Full-length recombinant mesenchymal fibronectin reduces spreading and promotes condensation and chondrogenesis of limb mesenchymal cells

White, D.; Hershey, Howard P.; Moss, Jessica; Daniels, Heather; Tuan, Rocky S.; Bennett, Vickie D.

doi:10.1046/j.1432-0436.2003.7104502.x

Cited by 41 publications

(29 citation statements)

References 65 publications

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“…Fibronectin is present in areas of chick limbs where condensed cells are differentiating, as well as in growth plate cartilage in chick and mouse (Bobick et al, 2009;Gehris et al, 1997;Imai et al, 2007;Melnick et al, 1981;Singh and Schwarzbauer, 2012, and our unpublished results). Fibronectin splice variants also change during condensation and differentiation, although what specific functions these variants perform has not been fully elucidated (White et al, 2003). Our results show that a crucial function for fibronectin in condensation is matrix assembly.…”

Section: Discussionmentioning

confidence: 77%

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

Singh

Schwarzbauer

2014

Journal of Cell Science

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Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix. Knockdown of fibronectin with small interfering RNAs (siRNAs) also blocked condensation. Fibrillar fibronectin matrix was detected prior to cell condensation, and its levels increased during and after condensation. Inhibition of fibronectin matrix assembly by use of the functional upstream domain (FUD) of adhesin F1 from Streptococcus pyogenes prevented cell condensation by MSCs and also by the chondrogenic cell line ATDC5. Our data show that cell condensation and induction of chondrogenesis depend on fibronectin matrix assembly and DTDST, and indicate that this transporter is required earlier in chondrogenesis than previously appreciated. They also raise the possibility that certain of the skeletal defects in DTD patients might derive from the link between DTDST, fibronectin matrix and condensation.

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Section: Discussionmentioning

confidence: 77%

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

Singh

Schwarzbauer

2014

Journal of Cell Science

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“…1B). The importance of this ECM for cell condensation and subsequent differentiation is evident from knockdown or blocking experiments in which targeting fibronectin, versican or collagen causes defects in chondrogenesis (Kamiya et al, 2006;White et al, 2003;Wilson et al, 2011). As differentiation proceeds, a matrix that is rich in fibronectin and type I collagen is replaced with one that contains type II collagen and aggrecan as the main components (Bobick et al, 2009;Sundelacruz and Kaplan, 2009).…”

Section: Steps Involved In Chondrogenesismentioning

confidence: 99%

“…Fibronectin containing both EIIIA and EIIIB is prevalent in the developing mesenchyme (Bennett et al, 1991), and antibody-blocking experiments have indicated that fibronectin containing the EIIIA exon participates in cell condensation (Gehris et al, 1997). During differentiation, inclusion of the EIIIA exon is reduced both in vivo and in vitro (Gehris et al, 1996), such that mRNA of cartilage fibronectin includes exon EIIIB but not exon EIIIA (White et al, 2003). This specific pattern of fibronectin transcript splicing suggests that the balance of isoforms contributes to chondrogenesis, but their exact functions remain to be determined.…”

Section: Ecm Deposition During Chondrogenesismentioning

confidence: 99%

Fibronectin and stem cell differentiation – lessons from chondrogenesis

Singh

Schwarzbauer

2012

Journal of Cell Science

168

156

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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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“…FN is involved in cell adhesion, migration, and ECM accumulation in processes such as embryogenesis, wound healing, blood coagulation, host defense, and metastasis. Various isoforms are produced from a single FN gene, and full length recombinant FN reduces spreading and promotes the condensation and chondrogenesis of limb mesenchymal cells (26). FN expression is increased in areas of cellular condensation that are decreased as cytodifferentiation proceeds (27,28).…”

Section: Discussionmentioning

confidence: 99%

Activation of epidermal growth factor receptor gene is involved in transforming growth factor-β-mediated fibronectin expression in a chondrocyte progenitor cell line

Takeda

Inoue²,

Kutsuna³

et al. 2010

Int J Mol Med

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Abstract. Chondrocytes produce many types of ECM to maintain elasticity and plasticity in articular cartilage of revolute joints. Both transforming growth factor ß (TGF-ß) and bone morphogenetic proteins (BMPs) induce extracellular matrix proteins such as type II·1 collagen and aggrecan during chondrogenic differentiation in vitro. However, differences in the matrix gene expression pattern by the stimulation of TGF-ßs and BMPs remains unclear. In the present study, we created a customized PCR-based ECM array to investigate the pattern of ECM expression genes in the chondrocyte progenitor cell line ATDC5, that was stimulated by TGF-ßs or BMPs. Fibronectin (Fn) expression was drastically induced after TGF-ß stimulation, but not BMP-4. Epidermal growth factor receptor (Egfr) gene was also significantly activated in TGF-ß1-induced chondrogenic differentiation as compared to BMP-4-mediated differentiation. Furthermore, EGFRknockdown assay of the cells showed decreasing Fn expression during TGF-ß1-induced chondrogenic differentiation. These data indicated that Egfr gene activation by TGF-ß is involved in the differences in the expression of cellular matrix genes such as Fn, as compared to the expression pattern induced by BMPs.

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Functional analysis of fibronectin isoforms in chondrogenesis: Full-length recombinant mesenchymal fibronectin reduces spreading and promotes condensation and chondrogenesis of limb mesenchymal cells

Cited by 41 publications

References 65 publications

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

Fibronectin and stem cell differentiation – lessons from chondrogenesis

Activation of epidermal growth factor receptor gene is involved in transforming growth factor-β-mediated fibronectin expression in a chondrocyte progenitor cell line

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