Site-1 protease is essential for endochondral bone formation in mice

Site-1 protease (S1P) has an essential function in the conversion of latent, membrane-bound transcription factors to their free, active form. In mammals, abundant expression of S1P in chondrocytes suggests an involvement in chondrocyte function. To determine the requirement of S1P in cartilage and bone development, we have created cartilage-specific S1P knockout mice (S1P(cko)). S1P(cko) mice exhibit chondrodysplasia and a complete lack of endochondral ossification even though Runx2 expression, Indian hedgehog signaling, and osteoblastogenesis is intact. However, there is a substantial increase in chondrocyte apoptosis in the cartilage of S1P(cko) mice. Extraction of type II collagen is substantially lower from S1P(cko) cartilage. In S1P(cko) mice, the collagen network is disorganized and collagen becomes entrapped in chondrocytes. Ultrastructural analysis reveals that the endoplasmic reticulum (ER) in S1P(cko) chondrocytes is engorged and fragmented in a manner characteristic of severe ER stress. These data suggest that S1P activity is necessary for a specialized ER stress response required by chondrocytes for the genesis of normal cartilage and thus endochondral ossification.

Coronary aneurysm formation in a patient early after everolimus-eluting stent implantation

Coronary aneurysm formation after drug-eluting stent (DES) implantation is a rare complication with late stent thrombosis as a potentially fatal sequela. One possible mechanism involved in aneurysm formation is thought to be late-acquired stent malapposition due to a local inflammatory response to the polymer and/or the drug. Coronary aneurysm formation has been documented with sirolimus- and paclitaxel-eluting stents. We report a case of coronary aneurysm formation in a patient with an everolimus-eluting stent (EES; Xience(R) Abbott Vascular, Redwood City, California) relatively early (3 months) after stent implantation. This case illustrates that even with second-generation DES like the EES, which is thought to be highly biocompatible, there can be adverse reactions to the polymer and/or to the drug.

Late-onset posttraumatic septal hematoma and abscess formation in a six-year-old Tamil girl--case report and literature review

Nasal septal hematoma with abscess (NSHA) is an uncommon complication of trauma and studies on children are especially rare. We discuss the case of a 6-year-old girl, who was initially evaluated independently by three doctors for minor nasal trauma but had to be re-hospitalized 6 days later with NSHA. Although septal hematoma had initially been excluded (5, 7 and 24 hours after trauma), a secondary accumulation of blood seems to have occured. Delayed hematoma formation has been described in the orbit as a result of possible venous injuries after endoscopic sinus surgery. However, such an observation is new for septal hematoma in children. Thus, we recommend re-evaluation for septal hematoma 48h to 72h after paediatric nasal trauma. Such a scheduled re-examination offers a chance to treat delayed subperichondral hematoma on time before almost inevitable superinfection leads to abscess formation and destruction of the nasal infrastructure. We suggest that parents should be vigilant for delayed nasal obstruction as possible herald of hematoma accumulation within the first week.

Long-term reaction to bone cement in osteoporotic bone: new bone formation in vertebral bodies after vertebroplasty

Elderly patients frequently suffer from osteoporotic vertebral fractures resulting in the need of vertebroplasty or kyphoplasty. Nevertheless, no data are available about the long-term consequences of cement injection into osteoporotic bone. Therefore, the aim of the present study was to evaluate the long-term tissue reaction on bone cement injected to osteoporotic bone during vertebroplasty. The thoracic spine of an 80-year-old female was explanted 3.5 years after vertebroplasty with polymethylmethacrylate. The treatment had been performed due to painful osteoporotic compression fractures. Individual vertebral bodies were cut in axial or sagittal sections after embedding. The sections were analysed using contact radiography and staining with toluidine blue. Furthermore, selected samples were evaluated with scanning electron microscopy and micro-compted tomography (in-plane resolution 6 microm). Large amounts of newly formed callus surrounding the injected polymethylmethacrylate were detected with all imaging techniques. The callus formation almost completely filled the spaces between the vertebral endplate, the cancellous bone, and the injected polymethylmethacrylate. In trabecular bone microfractures and osteoclast lacuna were bridged or filled with newly formed bone. Nevertheless, the majority of the callus formation was found in the immediate vicinity of the polymethylmethacrylate without any obvious relationship to trabecular fractures. The results indicate for the first time that, contrary to established knowledge, even in osteoporosis the formation of large amounts of new bone is possible.

Apelin signaling modulates splanchnic angiogenesis and portosystemic collateral vessel formation in rats with portal hypertension

BACKGROUND/AIMS: Angiogenesis is a pathological hallmark of portal hypertension. Although VEGF is considered to be the most important proangiogenic factor in neoangiogenesis, this process requires the coordinated action of a variety of factors. Identification of novel molecules involved in angiogenesis is highly relevant, since they may represent potential new targets to suppress pathological neovascularization in angiogenesis-related diseases like portal hypertension. The apelin/APJ signaling pathway plays a crucial role in angiogenesis. Therefore, we determined whether the apelin system modulates angiogenesis-driven processes in portal hypertension. METHODS: Partial portal vein-ligated rats were treated with the APJ antagonist F13A for seven days. Splanchnic neovascularization and expression of angiogenesis mediators (Western blotting) was determined. Portosystemic collateral formation (microspheres), and hemodynamic parameters (flowmetry) were also assessed. RESULTS: Apelin and its receptor APJ were overexpressed in the splanchnic vasculature of portal hypertensive rats. F13A effectively decreased, by 52%, splanchnic neovascularization and expression of proangiogenic factors VEGF, PDGF and angiopoietin-2 in portal hypertensive rats. F13A also reduced, by 35%, the formation of portosystemic collateral vessels. CONCLUSIONS: This study provides the first experimental evidence showing that the apelin/APJ system contributes to portosystemic collateralization and splanchnic neovascularization in portal hypertensive rats, presenting a potential novel therapeutic target for portal hypertension.

Which factors account for renal stone formation in cystic fibrosis?

Studies dealing with the increased tendency to stone formation noted in cystic fibrosis, focus on enteric hyperoxaluria. It is well recognized, however, that low urine volume, hypocitraturia and perhaps even hypercalciuria are further risk factors for stone formation.

Mechano-Chemical Aspects of Organ Formation in Arabidopsis thaliana: The Relationship between Auxin and Pectin

How instructive signals are translated into robust and predictable changes in growth is a central question in developmental biology. Recently, much interest has centered on the feedback between chemical instructions and mechanical changes for pattern formation in development. In plants, the patterned arrangement of aerial organs, or phyllotaxis, is instructed by the phytohormone auxin; however, it still remains to be seen how auxin is linked, at the apex, to the biochemical and mechanical changes of the cell wall required for organ outgrowth. Here, using Atomic Force Microscopy, we demonstrate that auxin reduces tissue rigidity prior to organ outgrowth in the shoot apex of Arabidopsis thaliana, and that the de-methyl-esterification of pectin is necessary for this reduction. We further show that development of functional organs produced by pectin-mediated ectopic wall softening requires auxin signaling. Lastly, we demonstrate that coordinated localization of the auxin transport protein, PIN1, is disrupted in a naked-apex produced by increasing cell wall rigidity. Our data indicates that a feedback loop between the instructive chemical auxin and cell wall mechanics may play a crucial role in phyllotactic patterning.

The etiology of cleft palate formation in BMP7-deficient mice

Palatogenesis is a complex process implying growth, elevation and fusion of the two lateral palatal shelves during embryogenesis. This process is tightly controlled by genetic and mechanistic cues that also coordinate the growth of other orofacial structures. Failure at any of these steps can result in cleft palate, which is a frequent craniofacial malformation in humans. To understand the etiology of cleft palate linked to the BMP signaling pathway, we studied palatogenesis in Bmp7-deficient mouse embryos. Bmp7 expression was found in several orofacial structures including the edges of the palatal shelves prior and during their fusion. Bmp7 deletion resulted in a general alteration of oral cavity morphology, unpaired palatal shelf elevation, delayed shelf approximation, and subsequent lack of fusion. Cell proliferation and expression of specific genes involved in palatogenesis were not altered in Bmp7-deficient embryos. Conditional ablation of Bmp7 with Keratin14-Cre or Wnt1-Cre revealed that neither epithelial nor neural crest-specific loss of Bmp7 alone could recapitulate the cleft palate phenotype. Palatal shelves from mutant embryos were able to fuse when cultured in vitro as isolated shelves in proximity, but not when cultured as whole upper jaw explants. Thus, deformations in the oral cavity of Bmp7-deficient embryos such as the shorter and wider mandible were not solely responsible for cleft palate formation. These findings indicate a requirement for Bmp7 for the coordination of both developmental and mechanistic aspects of palatogenesis.