The control of chondrogenesis

Goldring, Mary B.; Tsuchimochi, Kaneyuki; Ijiri, Kosei

doi:10.1002/jcb.20652

Cited by 948 publications

(932 citation statements)

References 107 publications

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“…Both processes begin with stem cell proliferation and condensation (Karsenty and Wagner 2002;Goldring et al, 2006). During intramembranous ossification, these condensed MSCs differentiate directly into osteoblasts.…”

Section: Osteoblast and Chondrocyte Differentiation During Skeletogenmentioning

confidence: 99%

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

Kelly

Jacobs

2010

Birth Defects Research Pt C

216

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: Osteoblast and Chondrocyte Differentiation During Skeletogenmentioning

confidence: 99%

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

Kelly

Jacobs

2010

Birth Defects Research Pt C

216

152

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“…any of several levels of regulation, including splice variation, ubiquitination, acetylation, and phosphorylation, as well as functional control through various DNA binding partners and inhibitors (reviewed in Franceschi and Xiao, 2003;Iwamoto et al, 2003;Bae and Lee, 2005;Lengner et al, 2005;Goldring et al, 2006).…”

Section: Runx2 In Larval Xenopus 1651mentioning

confidence: 99%

“…However, neither species requires the gene product to be functional during early cartilage formation. Runx2Јs inactivity during amniote cartilage formation may be attributed to several different levels of regulation imposed on the gene product (Franceschi and Xiao, 2003;Xiao et al, 2003;Wang et al, 2004;Bae and Lee, 2005;Lengner et al, 2005;Goldring et al, 2006). A change in post-transcriptional modification of Runx2 or in the function of one of its co-factors may account for the possible evolutionary loss of the transcript's function during cartilage formation within the amniote lineage.…”

Section: The Evolution Of Cartilage Differentiationmentioning

confidence: 99%

Runx2 is essential for larval hyobranchial cartilage formation in Xenopus laevis

Kerney

Gross

Howard

2007

Developmental Dynamics

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The vertebrate transcription factor protein Runx2 is regarded as a "master regulator" of bone formation due to the dramatic loss of the osseous skeleton in the mouse homozygous knockout. However, Runx2 mRNA also is expressed in the pre-hypertrophic cartilaginous skeleton of the mouse and chicken, where its developmental function is largely unknown. Several tiers of Runx2 regulation exist in the mouse, any of which may account for its seeming biological inactivity during early stages of skeletogenesis. Unlike mouse and chicken, zebrafish require Runx2 function in early cartilage differentiation. The present study reveals that the earlier functional role of Runx2 in cartilage differentiation is shared between zebrafish and Xenopus. A combination of morpholino oligonucleotide injections and neural crest transplants indicate that Runx2 is involved in differentiation of the cartilaginous hyobranchial skeleton in the frog, Xenopus laevis. Additionally, in situ hybridizations show runx2 mRNA expression in mesenchymal precursors of the cartilaginous skull, which reveals the earliest pre-patterning of these cartilages described to date. The early distribution of runx2 resolves the homology of the larval suprarostral plate, which is one of the oldest controversies of anuran skull development. Together these data reveal a shift in Runx2 protein function during vertebrate evolution towards its exclusive roles in cartilage hypertrophy and bone differentiation within the amniote lineage. Developmental Dynamics 236:1650 -1662, 2007.

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“…Chondrogenesis is a complex series of events including rapid proliferation, condensation and nodule formation of chondroprogenitor cells that requires coordinated activation of many intracellular signalling pathways [11]. The SRY-type HMG box transcription factors Sox9, L-Sox5 and Sox6 are essential for the mRNA expression of cartilage matrix-specific proteins (e.g.…”

Section: Introductionmentioning

confidence: 99%

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Juhász

Matta

Somogyi

et al. 2014

Cellular Signalling

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Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrixproducing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesispromoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of the intervention. Our results indicate that proper mechanical stimuli augment in vitro cartilage formation via promoting both Juhász and Matta et al. 3 differentiation and matrix production of chondrogenic cells, and the opposing regulation of the PKA/CREB-Sox9 and the PP2A signalling pathways is crucial in this phenomenon.

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The control of chondrogenesis

Cited by 948 publications

References 107 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

Runx2 is essential for larval hyobranchial cartilage formation in Xenopus laevis

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

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