Pierrette Menuelle

Regulation by glucocorticoids of cell differentiation and insulin-like growth factor binding protein production in cultured fetal rat nasal chondrocytes.

Glucocorticoids (GCs) modulate insulin‐like growth factor action in cartilage through mechanisms that are complex and insufficiently defined, especially in the context of cranio‐facial growth. Because the family of IGF‐binding proteins (IGFBP‐1 to ‐6) is important in the regulation of IGF availability and bioactivity, we examined the effect of GCs on chondrocyte differentiation in correlation with IGFBP production in cultured fetal rat chondrocytes isolated from nasal septum cartilage of fetal rat. Dexamethasone (DEX) effects were tested before and at the onset of extracellular matrix maturation. DEX induced a dose‐dependent increase in the size of cartilage nodule formed, 45Ca incorporation into extracellular matrix, alkaline phosphatase activity, and sulfatation of glycosaminoglycans, maximal effects being obtained with a 10‐mM DEX concentration. The IGFBPs produced by cultured chondrocytes were characterized in culture medium which had been conditioned for 24 h under serum‐free conditions by these cells. Western ligand blotting with a mixture of [125I]IGF‐I and ‐II revealed bands of 20, 24, 29, a 31–32 kDa doublet and a 39–41 kDa triplet which were differently regulated by DEX. Immunoblotting showed that following DEX exposure, IGFBP‐3 and ‐6 were up‐regulated whereas IGFBP‐2, ‐5, and the 24 kDa band were down‐regulated. The effect of DEX on both differentiation and IGFBP production showed a same dependence, and developed when extracellular matrix maturation had been just induced. The results obtained in this chondrocyte culture system show that production of IGFBPs is modulated by DEX at physiological concentrations thus regulating IGF availability and action, a control which could promote the primordial role of the rat nasal septum in craniofacial growth. J. Cell. Biochem. 88: 911–922, 2003.

Compared roles of glucose, galactose and fructose as glycogen precursors during the acute response to insulin in cultured rat foetal hepatocytes.

1. The efficiency of the contribution of hexoses to basal- and stimulated-glycogenesis, when studied in cultured 18 day-old rat foetal hepatocytes in the presence of glucose, was as follows: galactose greater than glucose greater than fructose. 2. Glucose deprivation had opposite effects on the contributions of [14C]galactose (decreased) and [14C]fructose (increased) to glycogenesis, which occurred independently of insulin and were reversed by glucose concentrations as low as 30-100 microM. 3. The stimulation of glycogenesis by insulin measured with [14C]glucose (3.2-fold) was superior to that obtained with either [14C]galactose or [14C]fructose (2.7-fold in both cases), which revealed a specific beneficial effect of insulin on glucose contribution.

Differences between glucose and insulin stimulation of glycogenesis in cultured fetal hepatocytes.

The glycogenic effects of a glucose load (15 mM) and/or insulin (10 nM) were studied in 18-day-old fetal rat hepatocytes after 2 days of culture when medium contained 4 mM glucose. A glucose load led to a stimulation of [14C]glucose glycogen labelling (20 min) earlier than with insulin (30-40 min); maximal stimulations were 3-fold after 1 h for the glucose load and 5-fold after 2-3 h for insulin. Simultaneous addition of the two agents produced synergic effects. When insulin was added 4 h after a glucose load (or vice versa), a second glycogenic response was elicited: a further addition of the same glycogenic agent was ineffective. The early glycogenic effects (up to 2 h) also occurred in the presence of 10 microM cycloheximide, with, however, some decrease of insulin stimulation. The contribution of medium glucose to the glycogen formed for 2 days (67% in the absence of glycogenic agent) was clearly enhanced by a glucose load and to a lesser degree by insulin after a 4-h exposure (83 and 71%, respectively). This was accompanied by a related modification of the participation of glucogenic precursors such as fructose and galactose. Thus, acute glycogenic response to glucose and insulin appeared both synergic and independent, and quite different in several aspects in cultured fetal hepatocytes.

Endocrinopathies and craniofacial dysmorphia: what can the orthodontist learn?: Première partie

Resume Le role des facteurs hormonaux et des genes dans le processus de developpement et de maturation squelettique est determinant ; leurs interventions dans les mecanismes de l’odontogenese ainsi que dans la regulation du metabolisme phosphocalcique expliquent la frequence des manifestations dento-maxillo-faciales lors de troubles endocriniens. Les repercussions cranio-faciales d’anomalies endocriniennes survenant dans le cadre d’anomalies genetiques sont tout d’abord presentees. Les syndromes evoques sont pour certains connus de l’orthodontiste, comme le syndrome de Turner ou meconnus comme le syndrome NEM 2B, dont l’expression bucco linguale precoce fait du chirurgien-dentiste ou de l’orthodontiste, l’un des premiers praticiens a pouvoir le diagnostiquer. D’autre part sont etudiees les manifestations cranio-faciales et buccales des endocrinopathies acquises. L’interet de ce travail est de permettre aux orthodontistes de reconnaitre les signes cliniques associes a la plupart des troubles endocriniens, afin d’orienter ces jeunes patients chez un specialiste, si le diagnostic n’a pas ete deja etabli, ou de prendre en compte ces anomalies dans le diagnostic et le plan de traitement orthopedique et orthodontique. L’approfondissement de nos connaissances orthodontiques et medicales aidera a completer l’anamnese, a affiner les diagnostics et a adapter les therapeutiques, grâce une « fertilization interdisciplinaire ».Resume Le role des facteurs hormonaux et des genes dans le processus de developpement et de maturation squelettique est determinant ; leurs interventions dans les mecanismes de l’odontogenese ainsi que dans la regulation du metabolisme phosphocalcique expliquent la frequence des manifestations dento-maxillo-faciales lors de troubles endocriniens. Les repercussions cranio-faciales d’anomalies endocriniennes survenant dans le cadre d’anomalies genetiques sont tout d’abord presentees. Les syndromes evoques sont pour certains connus de l’orthodontiste, comme le syndrome de Turner ou meconnus comme le syndrome NEM 2B, dont l’expression bucco linguale precoce fait du chirurgien-dentiste ou de l’orthodontiste, l’un des premiers praticiens a pouvoir le diagnostiquer. D’autre part sont etudiees les manifestations cranio-faciales et buccales des endocrinopathies acquises. L’interet de ce travail est de permettre aux orthodontistes de reconnaitre les signes cliniques associes a la plupart des troubles endocriniens, afin d’orienter ces jeunes patients chez un specialiste, si le diagnostic n’a pas ete deja etabli, ou de prendre en compte ces anomalies dans le diagnostic et le plan de traitement orthopedique et orthodontique. L’approfondissement de nos connaissances orthodontiques et medicales aidera a completer l’anamnese, a affiner les diagnostics et a adapter les therapeutiques, grâce une « fertilization interdisciplinaire ».