IGF expression patterns and regulation in growth plate chondrocytes

Schlegel, Werner; Halbauer, Daniel; Raimann, Adalbert; Albrecht, Christian; Scharmer, Daniela; Sagmeister, Susanne; Helmreich, M.; Häusler, Gabriele; Egerbacher, Monika

doi:10.1016/j.mce.2010.06.005

Cited by 16 publications

(11 citation statements)

References 40 publications

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“…13,31 Overall, these studies highlight the complicated nature of studying multiple growth factors in an in vitro model and although we chose two well-characterized growth factors we recognize that other growth factors and their isoforms (e.g., IGF-2) are likely to be involved in cartilage physiology and pathophysiology. 32,33 We have previously shown that oxygen is an important modulator of ion homeostasis in isolated articular chondrocytes 11,12 and here expand these observations with how growth factors and hypoxia might interact on H þ regulation. The mechanisms involved in H þ regulation in articular chondrocytes predominately act through Na þ /H þ exchange (NHE) 1 and our earlier work show intracellular acidosis occurring under hypoxic conditions through attenuation of NHE activity.…”

Section: Discussionsupporting

confidence: 64%

Growth factor regulation of intracellular pH homeostasis under hypoxic conditions in isolated equine articular chondrocytes

Milner

Smith

Robinson

et al. 2012

Journal Orthopaedic Research

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Hypoxia and acidosis are recognized features of inflammatory arthroses. This study describes the effects of IGF-1 and TGF-b 1 on pH regulatory mechanisms in articular cartilage under hypoxic conditions. Acid efflux, reactive oxygen species (ROS), and mitochondrial membrane potential were measured in equine articular chondrocytes isolated in the presence of serum (10% fetal calf serum), IGF-1 (1, 10, 50, 100 ng/ml) or TGF-b 1 (0.1, 1, 10 ng/ml) and then exposed to a short-term (3 h) hypoxic insult (1% O 2 ). Serum and 100 ng/ml IGF-1 but not TGF-b 1 attenuated hypoxic regulation of pH homeostasis. IGF-1 appeared to act through mitochondrial membrane potential stabilization and maintenance of intracellular ROS levels in very low levels of oxygen. Using protein phosphorylation inhibitors PD98059 (25 mM) and wortmannin (200 nM) and Western blotting, ERK1/2 and PI-3 kinase pathways are important for the effect of IGF-1 downstream to ROS generation in normoxia but only PI-3 kinase is implicated in hypoxia. These results show that oxygen and growth factors interact to regulate pH recovery in articular chondrocytes by modulating intracellular oxygen metabolites.

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Section: Discussionsupporting

confidence: 64%

Growth factor regulation of intracellular pH homeostasis under hypoxic conditions in isolated equine articular chondrocytes

Milner

Smith

Robinson

et al. 2012

Journal Orthopaedic Research

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“…All cDNA samples (2.4 µl in 20 µl) were analyzed in triplicate. The final numeric value was calculated by the ΔΔCT method using a calibrator based on previous data on total IGF-1 expression in laser capture microdissected resting zone chondrocyte samples (12.86) [42]. The resulting values were expressed in arbitrary units.…”

Section: Methodsmentioning

confidence: 99%

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

et al. 2013

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Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

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“…Previous studies regarding the distribution of IGFs in the bones of piglets and mice, revealed localization within the growth plate (41,42). Igf1 and Igf2 mRNA was expressed throughout all zones, albeit Igf1 less extensively.…”

Section: Expression Levels Of Igf Genes and Proteins In Fetal Serumentioning

confidence: 98%

“…Igf1 and Igf2 mRNA was expressed throughout all zones, albeit Igf1 less extensively. Immunohistochemical techniques also revealed the expression of IGFs within the resting zone, the hypertrophic zone and the proliferative zone of the growth plate (41) (Fig. 1).…”

Section: Expression Levels Of Igf Genes and Proteins In Fetal Serumentioning

confidence: 99%

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review)

Agrogiannis

Sifakis

Patsouris

et al. 2014

Molecular Medicine Reports

117

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The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre-implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

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IGF expression patterns and regulation in growth plate chondrocytes

Cited by 16 publications

References 40 publications

Growth factor regulation of intracellular pH homeostasis under hypoxic conditions in isolated equine articular chondrocytes

Growth factor regulation of intracellular pH homeostasis under hypoxic conditions in isolated equine articular chondrocytes

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review)

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