PKCdelta is a positive regulator of chondrogenesis in chicken high density micromass cell cultures

Matta, Csaba; Juhász, Tamás; Szíjgyártó, Zsolt; Kolozsvári, Bernadett; Somogyi, Csilla; Nagy, Gábor; Gergely, Pál; Zákány, Róza

doi:10.1016/j.biochi.2010.09.005

Cited by 15 publications

(13 citation statements)

References 43 publications

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“…The three MAPK pathways contribute to the regulation of chondrogenesis to a various extent: while JNKs seem not to be involved in this process, p38s and ERKs are key regulators of chondrogenic differentiation; in chicken HDC, an opposing role of p38 and ERK has been reported: while the p38 MAPK pathway promotes, activation of the MEK/ERK pathway represses in vitro chondrogenesis (31). The results of our laboratory also confirmed the negative role of the ERK1/2 pathway in the regulation of in vitro chondrogenesis in the same model (22,32).…”

Section: Chondrogenesis Is Regulated By Interplay Between Numerous Insupporting

confidence: 78%

Calcium signalling in chondrogenesis implications for cartilage repair

Matta¹

2013

Front Biosci

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Undifferentiated mesenchymal stem cells (MSCs) represent an important source for cell-based tissue regeneration techniques that require differentiation towards specific lineages, including chondrocytes. Chondrogenesis, the process by which committed mesenchymal cells differentiate into chondrocytes, is controlled by complex but not yet completely understood mechanisms that involve many components, including intracellular signalling pathways, as well as plasma membrane receptors and ion channels. Some of these signalling components are Ca2+ sensitive. Although the Ca2+-signalling toolkit of undifferentiated MSCs and mature chondrocytes are extensively studied, the adaptation of these components during differentiation and their role in chondrogenesis is not adequately established. In this review, various aspects of Ca2+ signalling are discussed in MSCs and in mature chondrocytes including spatial and temporal aspects, as well as Ca2+ entry and elimination processes, with implications for their involvement in chondrogenesis. A better understanding of these pathways is envisaged to provide a more efficient differentiation of MSCs towards chondrocytes that may lead to the development of better cartilage tissue engineering techniques.

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Section: Chondrogenesis Is Regulated By Interplay Between Numerous Insupporting

confidence: 78%

Calcium signalling in chondrogenesis implications for cartilage repair

Matta¹

2013

Front Biosci

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“…Total cell lysates for Western blot analyses were prepared as previously described [30]. 40 μg protein was separated in 7.5% SDS-polyacrylamide gels for the detection of Sox9, P-Sox9, HAS2, HAS3, CREB, P-CREB, PKA Cα, PP2A/C, aggrecan and GAPDH.…”

Section: Sds-page and Western Blot Analysismentioning

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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“…In this regard, an emblematic example of convergent but independent effects of Rottlerin and PKC δ downregulation is the recent study by Matta et al [16] performed in chicken chondrogenic mesenchymal cells. The authors found that both PKC δ silencing and 2.5–10 μ M Rottlerin (Sigma) decreased the protein levels of Sox9, the major cartilage-specific transcription factor, and impaired cartilage matrix production.…”

Section: Rottlerin Usage: the Open Debate On Selectivitymentioning

confidence: 99%

Rottlerin and Cancer: Novel Evidence and Mechanisms

Maioli

Torricelli

Valacchi

2012

The Scientific World Journal

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Because cancers are caused by deregulation of hundreds of genes, an ideal anticancer agent should target multiple gene products or signaling pathways simultaneously. Recently, extensive research has addressed the chemotherapeutic potential of plant-derived compounds. Among the ever-increasing list of naturally occurring anticancer agents, Rottlerin appears to have great potentiality for being used in chemotherapy because it affects several cell machineries involved in survival, apoptosis, autophagy, and invasion. The underlying mechanisms that have been described are diverse, and the final, cell-specific, Rottlerin outcome appears to result from a combination of signaling pathways at multiple levels. This paper seeks to summarize the multifocal signal modulatory properties of Rottlerin, which merit to be further exploited for successful prevention and treatment of cancer.

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PKCdelta is a positive regulator of chondrogenesis in chicken high density micromass cell cultures

Cited by 15 publications

References 43 publications

Calcium signalling in chondrogenesis implications for cartilage repair

Calcium signalling in chondrogenesis implications for cartilage repair

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

Rottlerin and Cancer: Novel Evidence and Mechanisms

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