Signaling mechanisms leading to regulation of proliferation and differentiation of the mesenchymal chondrogenic cell line RCJ3.1C5.18 in response to IGF-I

Ciarmatori, Sonia; Kiepe, Daniela; Haarmann, Anke; Huegel, Ulrike; Tönshoff, Burkhard

doi:10.1677/jme.1.02179

Cited by 29 publications

(25 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differentiation of RCJ cells was promoted by incubating the cells with β-glycerophosphate and ascorbic acid from day 4 of culture, as described in the Methods section. To evaluate the effect of proinflammatory cytokines on IGF-I-induced chondrocyte differentiation, RCJ cells were cultured in differentiating medium from day 4 of culture until day 14, followed by serum deprivation for 12 h and treatment with IGF-I (60 ng/ ml) and the indicated proinflammatory cytokines for additional 24 h. Exogenous IGF-I enhanced the expression of Ihh and collagen type X, two markers of terminally differentiated chondrocytes, four to sevenfold (Figure 5), consistent with our previous observations (7). While IL-6 and IL-1β reduced IGF-I-induced Ihh expression by ~60%, TNF-α completely abolished IGF-I-induced Ihh expression (Figure 5a).…”

Section: Proinflammatory Cytokines Inhibit Igf-i-stimulated Cell Diffsupporting

confidence: 89%

“…The main finding of the this study is that the proinflammatory cytokines IL-1β, IL-6, and TNF-α attenuate the mitogenic and differentiation-enhancing effect of IGF-I in growth plate chondrocytes and that these inhibitory effects are associated with a reduced phosphorylation of key signaling molecules of the PI-3 kinase and MAPK/ERK1/2 signaling pathways, which are critical for IGF-I signaling in these cells (7). Our data give a mechanistic explanation for the reduced biological activity of IGF-I in the presence of proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 75%

“…18, that two canonical pathways, the phosphatidylinositol-3 (PI-3)-kinase and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ ERK)1/2 pathway, mediate the mitogenic response to IGF-I. When chondrocytes progress from proliferating cells to early and terminal differentiating cells, they progressively inactivate IGF-I-related intracellular signaling pathways, and only the PI-3 kinase pathway remains operative for IGF-I signaling (7).…”

mentioning

confidence: 99%

“…Cells were fed at days 7 and 11 of culture and monitored over a total period of 14 d. RCJ cells are capable of differentiating spontaneously from displayed cuboidal-shaped isolated chondrocytes to cartilage nodules over 14 d of culture in differentiating medium in the presence of dexamethasone (20). At day 4 of culture, the cells represent proliferating chondrocytes (7). Prior to incubating the cells with cytokines and/or IGF-I, RCJ3.1C5.18 cells were cultured in serumfree medium for 12 h. …”

mentioning

confidence: 99%

See 3 more Smart Citations

Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

et al. 2014

View full text Add to dashboard Cite

Section: Proinflammatory Cytokines Inhibit Igf-i-stimulated Cell Diffsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 75%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

et al. 2014

View full text Add to dashboard Cite

“…IGF-I stimulates rat growth plate chondrocyte proliferation by activating both the MAPK and the PI3K pathways (36), which induces proliferation of RCJ3.1C5.18 and ATDC5 cells (mesenchymal cells with chondrogenic potential) through the MAPK (37,38) as well as the PI3K, the PKA, and the PKC pathways (37). Regarding the effects of IGF-I on chondrocyte terminal differentiation and apoptosis, they both appear to be primarily mediated by the PI3K/Akt signaling pathway (36 -39).…”

Section: Discussionmentioning

confidence: 99%

Stimulatory Effects of Insulin-like Growth Factor-I on Growth Plate Chondrogenesis Are Mediated by Nuclear Factor-κB p65

Fadoju

Rezvani

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Insulin-like growth factor-I (IGF-I) is an important regulator of endochondral ossification. However, little is known about the signaling pathways activated by IGF-I in growth plate chondrocytes. We have previously shown that NF-B-p65 facilitates growth plate chondrogenesis. In this study, we first cultured rat metatarsal bones with IGF-I and/or pyrrolidine dithiocarbamate (PDTC), a known NF-B inhibitor. The IGF-I-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by PDTC. In rat growth plate chondrocytes, IGF-I induced NF-B-p65 nuclear translocation. The inhibition of NF-B-p65 expression and activity (by p65 short interfering RNA and PDTC, respectively) in chondrocytes reversed the IGF-I-mediated induction of cell proliferation and differentiation and the IGF-I-mediated prevention of cell apoptosis. Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of IGF-I on NF-B activation. In conclusion, our findings indicate that IGF-I stimulates growth plate chondrogenesis by activating NF-B-p65 in chondrocytes. IGF-I2 is a key regulator of longitudinal bone growth, with such role being exerted both during intrauterine and extrauterine life. Knock-out mice for IGF-I exhibit intrauterine growth retardation and experience a subnormal postnatal growth rate (1). A similar growth pattern has been described in a child born with a homozygous IGF-I deletion (2).The fact that IGF-I null mice have a reduced growth plate height clearly suggests a facilitatory role for IGF-I on growth plate chondrogenesis and, in turn, on longitudinal bone growth. The presence of the IGF-I receptor in growth plate chondrocytes also suggests that IGF-I facilitates longitudinal bone growth directly at the growth plate (3, 4). However, little is known about the specific molecular mechanisms responsible for the IGF-I-mediated induction of growth plate chondrogenesis.Mammalian NF-B is a group of transcription factors, including seven members, p65 (RelA), c-Rel, RelB, p50/p105 (NF-B1), and p52/p100 (NF-B2) (5). Upon activation by a wide variety of stimuli (proinflammatory cytokines, growth factors, and viral proteins), NF-B translocates to the nucleus, where it modulates the expression of target genes involved in cell growth, survival, adhesion, and death (6, 7). These target genes include anti-apoptotic (8) as well as pro-apoptotic ones (9), suggesting that the effects of NF-B on cell growth and survival may depend on the cell type and on the nature of the extracellular stimuli.Previous evidence indicates that NF-B exerts a regulatory role in bone growth and development. Mice deficient in both the NF-B subunits p50 and p52 have retarded growth and shortened long bones (10), suggesting that NF-B may be involved in bone formation and growth. In addition, we have recently shown that the NF-B subunit p65 has a facilitatory role on growth plate chondrogenesis (11). Because experimental evidence in a number of cell types suggests a functional interaction between IGF-I and NF-B (12-...

show abstract

Regulation of cartilage formation and maturation by mitogen‐activated protein kinase signaling

Bobick

Kulyk

2008

Birth Defects Research Pt C

View full text Add to dashboard Cite

The majority of bones comprising the adult vertebrate skeleton are generated from hyaline cartilage templates that form during embryonic development. A process known as endochondral ossification is responsible for the conversion of these transient cartilage anlagen into mature, calcified bone. Endochondral ossification is a highly regulated, multistep cell specification program involving the initial differentiation of prechondrogenic mesenchymal cells into hyaline chondrocytes, terminal differentiation of hyaline chondrocytes into hypertrophic chondrocytes, and finally, apoptosis of hypertrophic chondrocytes followed by bone matrix deposition. Recently, extensive research has been carried out describing roles for the three major mitogen-activated protein kinase (MAPK) signaling pathways, the extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-jun N-terminal kinase (JNK) pathways, in the successive stages of chondrogenic differentiation. In this review, we survey this research examining the involvement of ERK1/2, p38, and JNK pathway signaling in all aspects of the chondrogenic differentiation program from embryonic through postnatal stages of development. In addition, we summarize evidence from in vitro studies examining MAPK function in immortalized chondrogenic cell lines and adult mesenchymal stem cells. We also provide suggestions for future studies that may help ameliorate existing confusion concerning the specific roles of MAPK signaling at different stages of chondrogenesis.

show abstract

Signaling mechanisms leading to regulation of proliferation and differentiation of the mesenchymal chondrogenic cell line RCJ3.1C5.18 in response to IGF-I

Cited by 29 publications

References 52 publications

Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

Stimulatory Effects of Insulin-like Growth Factor-I on Growth Plate Chondrogenesis Are Mediated by Nuclear Factor-κB p65

Regulation of cartilage formation and maturation by mitogen‐activated protein kinase signaling

Contact Info

Product

Resources

About