Protein Kinase C Regulates Chondrogenesis of Mesenchymes via Mitogen-activated Protein Kinase Signaling

Chang, Sung-Hee; Oh, Chun-Do; Yang, Myung-Soon; Kang, Shin‐Sung; Lee, Young-Sup; Sonn, Jong-Kyung; Chun, Jang‐Soo

doi:10.1074/jbc.273.30.19213

Cited by 91 publications

(169 citation statements)

References 40 publications

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“…Of these, PKC␣ exhibits the most marked expression and activation during chondrogenesis. Since the selective inhibition or down-regulation of PKC␣ is sufficient to block differentiation of mesenchymal cells (16,18,19), increased expression of this protein appears to be pivotal in the chondrogenesis process. PKC regulates expression of cell adhesion molecules, such as N-cadherin, fibronectin, and its receptor ␣ 5 ␤ 1 integrin, and hence controls progression of precartilage condensation to cartilage nodules (16).…”

mentioning

confidence: 99%

“…The PKC multigene family comprises 11 known isoforms (20). Multiple PKC isoforms such as ␣, ⑀, , and / are expressed in differentiating chick limb mesenchymal cells (16). Of these, PKC␣ exhibits the most marked expression and activation during chondrogenesis.…”

mentioning

confidence: 99%

“…We previously showed that chondrogenic differentiation of chick limb bud mesenchymal cells is regulated by complex protein kinase signaling cascades involving protein kinase C (PKC) (15,16), ERK-1 (16,17), p38 mitogen-activated protein (MAP) kinase (17,18), and protein kinase A (19). PKC appears to positively regulate chondrogenesis of mesenchymal cells (15,16). The PKC multigene family comprises 11 known isoforms (20).…”

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confidence: 99%

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Maintenance of Differentiated Phenotype of Articular Chondrocytes by Protein Kinase C and Extracellular Signal-regulated Protein Kinase

Yoon¹,

Kim²,

Oh³

et al. 2002

Journal of Biological Chemistry

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The differentiated phenotype of chondrocyte is rapidly lost during in vitro culture by a process designated "dedifferentiation." In this study, we investigate the roles of protein kinase C (PKC) and extracellular signalregulated protein kinase (ERK) in the maintenance of the differentiated chondrocyte phenotype. Chondrocytes isolated from rabbit articular cartilage underwent dedifferentiation upon serial monolayer culture with cessation of type II collagen expression and proteoglycan synthesis, which was reversed by culturing dedifferentiated cells in alginate gel. The expression pattern of PKC␣ was essentially the same as that of type II collagen during de-and redifferentiation, in that expression was decreased during dedifferentiation and increased during redifferentiation. In contrast to PKC␣, ERK activity increased 15-fold during dedifferentiation. This enhanced activity was terminated during redifferentiation. Down-regulation of PKC␣ in passage 0 chondrocytes resulted in dedifferentiation. However, overexpression of PKC␣ did not affect type II collagen levels, suggesting that PKC␣ expression is not sufficient to maintain the differentiated phenotype. However, inhibition of ERK by PD98059 enhanced type II collagen expression and proteoglycan synthesis in passage 0 cells, retarded dedifferentiation during monolayer cultures, and reversed dedifferentiation caused by downregulation of PKC. Unlike PKC-dependent ERK regulation of chondrogenesis, PKC and ERK independently modulated chondrocyte dedifferentiation, as confirmed by observations that PKC down-regulation and ERK inhibition did not alter ERK phosphorylation and PKC expression, respectively. In addition, expression of Ncadherin, ␣-catenin, and ␤-catenin, which are oppositely regulated to type II collagen during phenotype alterations, were modulated by PKC and ERK during chondrogenesis but not dedifferentiation, supporting distinct mechanisms for the regulation of chondrocyte differentiation and maintenance of differentiated phenotype by these two protein kinases.

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Maintenance of Differentiated Phenotype of Articular Chondrocytes by Protein Kinase C and Extracellular Signal-regulated Protein Kinase

Yoon¹,

Kim²,

Oh³

et al. 2002

Journal of Biological Chemistry

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165

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“…Consisting of a cascade of protein kinases, Raf, MAPK/ERK kinase (MEK) and ERK1/2, the ERK pathway mediates the effects of growth factors and cytokines through a plethora of downstream signalling pathways during chondrogenesis. While p38 clearly stimulates chondrogenesis in all experimental models studied [21,22], the ERK1/2 pathway has been reported to be both negative [23,24] and positive regulator [25,26] of chondrogenic differentiation, depending on the species, the differentiation stage, the embryonic origin of chondroprogenitor cells, and probably the context of other concurrently active/blocked signalling mechanisms [3]. Likewise, both chondrogenesis-promoting [27] and inhibitory [28] effects for the JNK pathway have been established.…”

Section: Ser/thr-specific Pks Regulate Chondrogenesismentioning

confidence: 98%

Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game

Matta

Mobasheri

Gergely

et al. 2014

Cellular Signalling

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“…For instance, both down-regulation of ERK1/2 and induction of p38 kinase activities are required for chondrogenic differentiation of mesenchymal cells (10,11), and activation of ERK1/2 in differentiated articular chondrocytes causes dedifferentiation (7). ERK1/2 and p38 kinase also oppositely regulate NOinduced dedifferentiation and apoptosis of chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of arginase II as a chondrocyte phenotype‐specific gene

Huh

Lee

et al. 2006

IUBMB Life

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SummaryWe have previously shown that activation of extracellular signalregulated protein kinase-1 and -2 (ERK1/2) causes chondrocyte dedifferentiation, which contributes to the destruction of arthritic cartilage. In the present study, we identified genes involved in the ERK1/2 regulation of chondrocyte dedifferentiation. Several genes were identified by subtractive hybridization, and, of these, arginase II was selected for further functional characterization. Similar to the pattern of type II collagen expression, which is a hallmark of chondrocyte differentiation, arginase II expression was increased during chondrogenesis of mesenchymal cells. The high expression level of arginase II was decreased during dedifferentiation of chondrocytes, whereas its expression was restored during redifferentiation of the dedifferentiated chondrocytes. Inhibition of ERK1/2 signaling in chondrocytes enhanced type II collagen expression with a concomitant increase in expression and activity of arginase II. However, ectopic expression of arginase II or inhibition of its activity did not affect chondrocyte differentiation. The results collectively indicate that expression of arginase II is specific to the chondrocyte phenotype, although the expression of arginase II alone is not sufficient for articular chondrocytes to maintain a differentiated phenotype. IUBMB Life, 58: 597-605, 2006

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Protein Kinase C Regulates Chondrogenesis of Mesenchymes via Mitogen-activated Protein Kinase Signaling

Cited by 91 publications

References 40 publications

Maintenance of Differentiated Phenotype of Articular Chondrocytes by Protein Kinase C and Extracellular Signal-regulated Protein Kinase

Maintenance of Differentiated Phenotype of Articular Chondrocytes by Protein Kinase C and Extracellular Signal-regulated Protein Kinase

Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game

Identification and characterization of arginase II as a chondrocyte phenotype‐specific gene

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