Growth hormone receptor signalling and actions in bone growth.

Growth hormone (GH) acts by binding to a membrane receptor that is part of the cytokine receptor superfamily. Ligand binding induces receptor dimerization leading to activation of the associated tyrosine kinase, Janus kinase (Jak) 2. Transphosphorylation of Jak2 occurs followed by tyrosine phosphorylation of the receptor, and numerous cytoplasmic proteins. Among these are the signal transducers and activators of transcription (Stat) proteins, as well as adaptor proteins leading to the activation of the Ras/mitogen-activated protein (MAP) kinase and the phosphatidyl-inositol-3'-kinase (PI 3-kinase) pathways. Activation of the GH receptor system is relatively transient, with several mechanisms being involved in down-regulation: internalization and degradation of the receptor and recruitment of phosphatases or specific inhibitors of the Jak-Stat pathway, the suppressors of cytokine signalling (SOCS) proteins. Finally, the use of the GH receptor knock-out mouse model has allowed us to dissect the role of this hormone in post-natal body growth and homeostasis.

Morphogenesis and renewal of hair follicles from adult multipotent stem cells.

The upper region of the outer root sheath of vibrissal follicles of adult mice contains multipotent stem cells that respond to morphogenetic signals to generate multiple hair follicles, sebaceous glands, and epidermis, i.e., all the lineages of the hairy skin. At the time when hair production ceases and when the lower region of the follicle undergoes major structural changes, the lower region contains a significant number of clonogenic keratinocytes, and can then respond to morphogenetic signals. This demonstrates that multipotent stem cells migrate to the root of the follicle to produce whisker growth. Moreover, our results indicate that the clonogenic keratinocytes are closely related, if not identical, to the multipotent stem cells, and that the regulation of whisker growth necessitates a precise control of stem cell trafficking.

Aortic stents covering the renal arteries ostia: an animal study.

PURPOSE: To evaluate the consequences of placing an aortic stent over the renal arteries. MATERIALS AND METHODS: The renal ostia of 11 pigs were covered by Strecker stents placed in the aorta. At 1 month, the degree of renal ostial stenosis was determined by means of angiography and gross pathologic and histologic examination. Any reduction in area of the renal ostia was considered significant. Preprocedure and 1-month serum creatinine levels were also examined. RESULTS: One stent migrated and was excluded from the study. There was one angiographic failure and, among the remaining 18 renal arteries evaluated, one was occluded, six were stenosed, and 11 were patent. Of the 10 samples available for pathologic examination, one was excluded from study because one stent was not fully deployed. A neointima was covering the struts crossing or encircling the renal arteries ostia with a mean area coverage of 43% +/- 30% (range, 0-84%). Serum creatinine levels rose from 71.1 mumol/L +/- 7.1 preoperatively to 94.2 mumol/L +/- 6.7 postoperatively (P < .01). CONCLUSION: An aortic stent placed over the renal arteries in pigs may compromise renal perfusion in the long-term because neointima tends to fill the spaces between the struts.

[Acceleration of the regeneration of skeletal muscles in adult rats by dextran derivatives]. / Accélération de la régénération d'un muscle squelettique de rat adulte par des dérivés de dextranes.

Dextran derivatives were obtained by controlled successive substitutions of carboxymethyl, carbomethyl-benzylamide and carboxymethyl-benzylamide sulfonate groups on glucose residues. Among these derivatives, RGT11 was selected since it mimicked some properties of heparin or heparan sulfate to stabilise and protect heparin binding growth factors such as FGFs and TGF-beta. Furthermore RGT11 inhibited plasmine and leukocyte elastase. In previous works, we have explained the healing effects of RGT obtained in skin or bone repair models by these protecting and inhibiting properties. We now present the results obtained after a single injection of RGT11 in a regenerating crushed extensor digitorum longus (EDL) muscle. After 8 days, RGT11 injected muscles contained 10 times the number of fibers than controlled injected muscles. Fibers were organized in bundles of normal size. Histological analysis indicated that regeneration was comparable to that observed after 3 weeks without RGT. Hence in vivo, RGT11 could act by protecting the heparin binding growth factors involved in the natural process of muscle regeneration and therefore favour their actions. This family of polymers should offer a new pharmaceutical potential for treating muscle atrophy and destruction and is worth studying further.