Leukaemia Inhibitory Factor (Lif) Is Expressed in Hypertrophic Chondrocytes and Vascular Sprouts During Osteogenesis

Grimaud, Eva; Blanchard, Frédéric; Charrier, Céline; Gouin, F.; Redini, F.; Heymann, Dominique

doi:10.1006/cyto.2002.2002

Cited by 27 publications

(19 citation statements)

References 38 publications

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“…Our studies identified three members of the GP-130 family of cytokines, namely interleukins -11,-6 ( Il11, Il6 ) and leukemia inhibitory factor ( Lif ), as part of the core enrichment group for cytokines (Table 6). Transgenic mice overexpressing Il-6 exhibit growth retardation, and LIF is thought to regulate the rate at which terminally differentiated cartilage is calcified and vascularized [71,72]. …”

Section: Resultsmentioning

confidence: 99%

Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development

et al. 2007

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Background: Glucocorticoids (GCs) are widely used anti-inflammatory drugs. While useful in clinical practice, patients taking GCs often suffer from skeletal side effects including growth retardation in children and adolescents, and decreased bone quality in adults. On a physiological level, GCs have been implicated in the regulation of chondrogenesis and osteoblast differentiation, as well as maintaining homeostasis in cartilage and bone. We identified the glucocorticoid receptor (GR) as a potential regulator of chondrocyte hypertrophy in a microarray screen of primary limb bud mesenchyme micromass cultures. Some targets of GC regulation in chondrogenesis are known, but the global effects of pharmacological GC doses on chondrocyte gene expression have not been comprehensively evaluated.

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Section: Resultsmentioning

confidence: 99%

Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development

et al. 2007

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“…Tyrosine phosphorylation is performed by a number of kinases, including TYK2, JAK1, and JAK2 [29, 37], which in turn can be activated by cytokines such as LIF and other IL6 family members [38, 39, 44]. LIF is constitutively expressed in growth plate chondrocytes [40] and osteoblasts [41], but is expressed at a low level in articular cartilage [42] and in bone marrow [43]. LIF is a member of the IL6 family of cytokines, which also includes IL6, IL11, OSM, CNTF, CTF1, and CLCF1.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of shortened bones in mucopolysaccharidosis VII

Metcalf

Zhang

Hilton

et al. 2009

Molecular Genetics and Metabolism

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Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease in which deficiency in β-glucuronidase results in glycosaminoglycan (GAG) accumulation in and around cells, causing shortened long bones through mechanisms that remain largely unclear. We demonstrate here that MPS VII mice accumulate massive amounts of the GAG chondroitin-4-sulfate (C4S) in their growth plates, the cartilaginous region near the ends of long bones responsible for growth. MPS VII mice also have only 60% of the normal number of chondrocytes in the growth plate and 55% of normal chondrocyte proliferation at 3 weeks of age. We hypothesized that this reduction in proliferation was due to C4S-mediated overactivation of fibroblast growth factor receptor 3 (FGFR3). However, MPS VII mice that were FGFR3-deficient still had shortened bones, suggesting that FGFR3 is not required for the bone defect. Further study revealed that MPS VII growth plates had reduced tyrosine phosphorylation of STAT3, a pro-proliferative transcription factor. This was accompanied by a decrease in expression of leukemia inhibitory factor (LIF) and other interleukin 6 family cytokines, and a reduction in phosphorylated tyrosine kinase 2 (TYK2), Janus kinase 1 (JAK1), and JAK2, known activators of STAT3 phosphorylation. Intriguingly, loss of function mutations in LIF and its receptor leads to shortened bones. This suggests that accumulation of C4S in the growth plate leads to reduced expression of LIF and reduced STAT3-tyrosine phosphorylation, which results in reduced chondrocyte proliferation and ultimately shortened bones.

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“…LIF is a cytokine that is expressed in terminally-differentiated growth plate chondrocytes [24] and signals through the gp130/LIFR complex. Homozygosity for loss of function mutations in the LIF receptor produces the recessively inherited skeletal dysplasia, Stuve-Wiedemann syndrome [25].…”

Section: Discussionmentioning

confidence: 99%

Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression

et al. 2007

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Background: Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate into chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18-22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed Celsius.

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Leukaemia Inhibitory Factor (Lif) Is Expressed in Hypertrophic Chondrocytes and Vascular Sprouts During Osteogenesis

Cited by 27 publications

References 38 publications

Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development

Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development

Mechanism of shortened bones in mucopolysaccharidosis VII

Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression

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