Induction of chondrogenesis in limb mesenchymal cultures by disruption of the actin cytoskeleton.

Zanetti, Nina C.; Solursh, Michael

doi:10.1083/jcb.99.1.115

Cited by 268 publications

(136 citation statements)

References 40 publications

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“…shown increase expression of SOX9 and its target genes collagen II and aggrecan (Woods et al, 2005;Woods and Beier 2006). In addition, treatment with cytochalasin, a cytoskeleton-interrupting reagent, promotes chondrogenesis of embryonic mesenchymal cells (Zanetti and Solursh 1984) and bone marrow stem cells (Lim et al, 2000). Similarly, treatment of murine embryonic stem cells with cytochalasin leads to actin filament disruption and subsequent reorganization into a peripheral distribution which results in a more rounded morphology (Zhang et al, 2006).…”

Section: Repairmentioning

confidence: 99%

The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

Kelly

Jacobs

2010

Birth Defects Research Pt C

213

152

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It is becoming increasingly clear that Mesenchymal Stem Cell (MSC) differentiation is regulated by mechanical signals. Mechanical forces generated intrinsically within the cell in response to its extracellular environment, and extrinsic mechanical signals imposed upon the cell by the extracellular environment, play a central role in determining MSC fate. This paper reviews chondrogenesis and osteogenesis during skeletogenesis, and then considers the role of mechanics in regulating limb development and regenerative events such as fracture repair. However, observing skeletal changes under altered loading conditions can only partially explain the role of mechanics in controlling MSC differentiation. Increasingly, understanding how epigenetic factors such as the mechanical environment regulate stem cell fate is undertaken using tightly controlled in vitro models. Factors such as bio-engineered surfaces, substrates and bioreactor systems are used to control the mechanical forces imposed upon, and generated within, MSCs. From these studies, a clearer picture of how osteogenesis and chondrogenesis of MSCs is regulated by mechanical signals is beginning to emerge. Understanding the response of MSCs to such regulatory factors is a key step towards understanding their role in disease and regeneration.3

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Section: Repairmentioning

confidence: 99%

The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

Kelly

Jacobs

2010

Birth Defects Research Pt C

213

152

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“…[10] A similar beneficial effect is also seen in limb mesenchymal chondrogenic cells in micromass in which actin filament disruption was found to enhance their differentiation into chondrocytes. [12] These studies demonstrate the importance of cytoskeletal development in regulating chondrocyte morphology and phenotype.…”

Section: Introductionmentioning

confidence: 99%

Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes

Kerr

Otani

Koyama

et al. 2008

Experimental Cell Research

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During maturation, chondrocytes undergo changes in morphology, matrix production, and gene expression; however, it remains unclear whether these are interrelated. In this study, we examined whether Rho GTPases were involved in these regulatory interplays. Levels of active Rho GTPases were assayed in immature and mature primary chondrocytes. We found that activation of Rac-1 and Cdc42 increased with maturation, whereas RhoA levels remained unchanged. GFP-tagged Rho GTPases tracked cellular localization. Rac-1 was enriched at the cell membrane where it co-localized with cortical actin, while RhoA and Cdc42 were cytoplasmic. To test the roles of Rac-1 in chondrocyte maturation, we force-expressed constitutively active or dominant negative forms of Rac-1 and assessed phenotypic consequences in primary chondrocytes. Activated Rac-1 expression induced chondrocyte enlargement and increased matrix metalloproteinase expression, which are characteristic of mature chondrocytes. Conversely, Rac-1 inactivation diminished adhesion, decreased alkaline phosphatase activity, and stimulated functions typical of immature chondrocytes. Exposure to a pro-maturation factor, Wnt3A, induced a flattened and enlarged morphology accompanied by peripheral Rac-1 rearrangement. Wnt3A stimulated Tiam1 expression and Rac-1 activation, while DN-Rac-1 inhibited Wnt3A-induced cell spreading. Our data provide strong evidence that Rac-1 coordinates changes in chondrocyte phenotype and function and stimulates the maturation process essential for skeletal development.

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“…Prostaglandin-mediated elevations in cAMP levels during condensation are involved in regulating chondrogenesis (3, 6, 11, 14, 16-18, 32, 33). A change in the shape of the cells from a flattened mesenchymal morphology to a rounded configuration also plays an important role in the process (2,41).…”

Section: T He Onset Of Cartilage Differentiation In the Developingmentioning

confidence: 99%

Collagen gene expression during limb cartilage differentiation.

Kosher¹,

Kulyk²,

Gay³

1986

The Journal of Cell Biology

227

128

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Abstract. As limb mesenchymal cells differentiate into chondrocytes, they initiate the synthesis of type II collagen and cease synthesizing type I collagen. Changes in the cytoplasmic levels of type I and type II collagen mRNAs during the course of limb chondrogenesis in vivo and in vitro were examined using cloned cDNA probes. A striking increase in cytoplasmic type II collagen m R N A occurs coincident with the crucial condensation stage of chondrogenesis in vitro, in which prechondrogenic mesenchymal cells become closely juxtaposed before depositing a cartilage matrix. Thereafter, a continuous and progressive increase in the accumulation of cytoplasmic type II coUagen m R N A occurs which parallels the progressive accumulation of cartilage matrix by ceils. The onset of overt chondrogenesis, however, does not involve activation of the transcription of the type II collagen gene. Low levels of type II collagen m R N A are present in the cytoplasm of prechondrogenic mesenchymal cells at the earliest stages of limb development, well before the accumulation of detectable levels of type II collagen. Type I collagen gene expression during chondrogenesis is regulated, at least in part, at the translational level. Type I collagen mRNAs are present in the cytoplasm of differentiated chondrocytes, which have ceased synthesizing detectable amounts of type I collagen. T HE onset of cartilage differentiation in the developinglimb is characterized by a transient cellular condensation or aggregation process in which prechondrogenic mesenchymal cells become closely juxtaposed to one another before initiating cartilage matrix deposition. During this process, a cell-cell interaction, cell shape change, or some other event occurs which is necessary to trigger the chondrogenic differentiation of the cells (15). The critical condensation process may be initiated, at least in part, by a progressive decrease in the accumulation of extracellular hyaluronate (20,35). Fibronectin and type I collagen have been implicated in the cell-cell interaction occurring during condensation (7, 21, 34). Prostaglandin-mediated elevations in cAMP levels during condensation are involved in regulating chondrogenesis (3, 6, 11, 14, 16-18, 32, 33). A change in the shape of the cells from a flattened mesenchymal morphology to a rounded configuration also plays an important role in the process (2, 41).Although considerable insight has been gained into the extracellular influences and intracellular regulatory molecules that are involved in regulating limb chondrogenesis, virtually nothing is known about the molecular mechanisms by which these factors directly influence the changes in gene activity that occur during cartilage differentiation. Prechondrogenic limb mesenchymal cells synthesize type I collagen (36). As the cells differentiate into chondrocytes, they initiate the synthesis of cartilage-characteristic type II collagen and cease synthesizing type I collagen (36). Thus the conversion of mesenchymal chondrogenic progenitor cells into chondrocytes i...

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Induction of chondrogenesis in limb mesenchymal cultures by disruption of the actin cytoskeleton.

Cited by 268 publications

References 40 publications

The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes

Collagen gene expression during limb cartilage differentiation.

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