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See detailDifferential signalling through ALK-1 and ALK-5 regulates leptin expression in Mesenchymal Stem Cells
Zeddou, M.; RELIC, Biserka ULg; MALAISE, Olivier ULg et al

in Stem Cells & Development (2012), 21(11), 1948-54

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little ... [more ▼]

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known on its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts. Here, we investigated leptin expression in MSC from bone marrow (BM-MSC), cord matrix (UMSC), and primary and dedifferentiated chondrocytes (DCH). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Interestingly, chondrocytes gained leptin expression progressively with dedifferentiation. This dedifferentiation was correlated with downregulation of ALK-5 expression, Smad2 phosphorylation (p-Smad2), and gain of ALK-1 expression and Smad1/5 phosphorylation (p-Smad1/5). TGF-β1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways. In BM-MSC, TGF-β1 increased p-Smad2 expression and markedly inhibited endogenous- and glucocorticoidinduced leptin expression, while ALK-5 inhibitor (SB431542) induced and restored this expression. In addition, both prednisolone and <br />SB431542 increased p-Smad1/5 expression. These results suggested ALK-5-Smad2 pathway as inhibitor of leptin expression, while ALK-1-Smad1/5 as activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-βRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC and UMSC that correlates to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin non-producer MSC for cell therapy protocols where leptin expression is not suitable. [less ▲]

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See detailComment j’explore ... une masse rétropéritonéale chez l’enfant
Malaise, Olivier ULg; Vandenbosch, Kristel ULg; Uyttebroeck, Anna et al

in Revue Médicale de Liège (2010), 65(3), 156-162

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. Wilms tumor and neuroblastoma, the most frequent, will be presented more in detail including their clinical and ... [more ▼]

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. Wilms tumor and neuroblastoma, the most frequent, will be presented more in detail including their clinical and biological characteristics, their diagnostic tests and their primary therapeutic treatments. [less ▲]

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See detailLes masses rétropéritonéales chez l’enfant : à propos d’une tumeur de Wilms et d’un neuroblastome
Malaise, Olivier ULg; Vandenbosch, Kristel ULg; Uyttebroeck, Anna et al

in Revue Médicale de Liège (2010), 65(3), 115-116

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. We present the case- reports of 2 children under the age of 5 years admitted to the University Hospital of Liège, one ... [more ▼]

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. We present the case- reports of 2 children under the age of 5 years admitted to the University Hospital of Liège, one with a Wilms tumor and one with a neuroblastoma. [less ▲]

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See detailElongator controls the migration and differentiation of cortical neurons through acetylation of a tubulin
Creppe, Catherine ULg; Malinouskaya, Lina ULg; Volvert, Marie-Laure ULg et al

in Cell (2009), 136

The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit histone acetyltransferase Elongator complex, which ... [more ▼]

The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit histone acetyltransferase Elongator complex, which contributes to transcript elongation, also regulates the maturation of projection neurons. Indeed, silencing of its scaffold (Elp1) or catalytic subunit (Elp3) cell-autonomously delays the migration and impairs the branching of projection neurons. Strikingly, neurons defective in Elongator show reduced levels of acetylated alpha tubulin. A direct reduction of alpha tubulin acetylation leads to comparable defects in cortical neurons and suggests that alpha tubulin is a target of Elp3. This is further supported by the demonstration that Elp3 promotes acetylation and counteracts HDAC6-mediated deacetylation of this substrate in vitro. Our results uncover alpha tubulin as a target of the Elongator complex and suggest that a tight regulation of its acetylation underlies the maturation of cortical projection neurons. [less ▲]

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See detailTraitements non hormonaux de l’ostéoporose postménopausique
Malaise, Olivier ULg; Neuprez, Audrey ULg; Reginster, Jean-Yves ULg

in Gynécologie Obstétrique & Fertilité (2008), 36

In the last decade, several medications have been registered and marketed in osteoporosis. They have demonstrated their antifracture efficacy. Subsequently, the clinical management of osteoporosis becomes ... [more ▼]

In the last decade, several medications have been registered and marketed in osteoporosis. They have demonstrated their antifracture efficacy. Subsequently, the clinical management of osteoporosis becomes more sophisticated and complex. Bisphosphonates (alendronate, risedronate, ibandronate, ibandronate and zoledronate) have demonstrated their efficacy on the axial and appendicular skeleton. On scientific grounds, it seems difficult to distinguish between them, in terms of efficacy and/or safety. A special interest should be focused on the optimisation of patients’ adherence, which remains poor with the daily and weekly formulations. Raloxifene, a selective estrogen receptor modulator, has shown antifracture efficacy at the level of the lumbar spine and, also, exerts collateral benefits on the breast. The peptides from the parathyroid hormone family are simulators of bone formation. They showed antifracture efficacy at the axial and appendicular skeleton. Due to their prohibitive costs, their use should be restricted to patients with severe osteoporosis. Strontium ranelate, with its unique mode of action combining inhibition of bone resorption and stimulation of bone formation, is characterized by a wide scatter of activity, both in terms of skeletal sites positively affected and of patients experiencing benefits of its administration. Currently, it is the only drug which has shown an extensive anti-fracture efficacy in elderly subjects over 80 years old. [less ▲]

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See detailStrontium ranelate normalizes bone mineral density in osteopenic patients
Malaise, Olivier ULg; Bruyère, Olivier ULg; Reginster, Jean-Yves ULg

in Aging Clinical & Experimental Research (2007), 19(4), 330-333

AIMS: To assess the capacity of strontium ranelate to restore normal bone mineral density (WHO definition: T-score >or=-1) in post-menopausal osteopenic women (T-score between -1 and -2.5) at baseline ... [more ▼]

AIMS: To assess the capacity of strontium ranelate to restore normal bone mineral density (WHO definition: T-score >or=-1) in post-menopausal osteopenic women (T-score between -1 and -2.5) at baseline. METHODS: Post-hoc analysis from SOTI and TROPOS studies of 1428 patients randomly assigned to receive either 2 g of strontium ranelate a day or placebo for three years. Bone mineral density was measured at baseline and each year for three years. Results were analyzed on an intention-to-treat basis. RESULTS: At lumbar spine, after one, two and three years of treatment with strontium ranelate, 26.4, 42.1 and 58.2% respectively of osteopenic patients normalized their bone mineral density, compared with 6.6, 8.9 and 11.9% in the placebo group (all p<0.001). At total hip, the percentage of patients normalizing their bone mineral density was 5.4, 10.0 and 19.6% in the strontium ranelate group and 1.8, 1.4 and 1.6% in the placebo one (all p<0.001). CONCLUSION: Strontium ranelate is able to normalize bone mineral density in a significant proportion of osteopenic patients after one, two and three years of treatment. The clinical relevance of these results should be confirmed by direct demonstration of the anti-fracture efficacy of strontium ranelate in osteopenic patients. [less ▲]

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See detailPrevalence of vitamin D inadequacy in European postmenopausal women
Bruyère, Olivier ULg; Malaise, Olivier ULg; Neuprez, A. et al

in Current Medical Research & Opinion (2007), 23(8), 1939-1944

Objective: Inadequate vitamin D level is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to ... [more ▼]

Objective: Inadequate vitamin D level is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to assess the prevalence of inadequate serum vitamin D levels in postmenopausal European women. There are no clear international agreements on what constitutes a level of vitamin D inadequacy, but recent publications suggest that the circulating level of vitamin D should be over 80 nmol/L or at least between 50 and 80 nmol/L. Material and methods: Assessment of 25-hydroxyvitamin D [25(OH)D] was performed in 8532 European postmenopausal women with osteoporosis or osteopenia. European countries included France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-offs of 25(OH)D inadequacy were fixed < 80 nmol/L and < 50 nmol/L. Results: Mean (SD) age of the patients was 74.2 (7.1) years, body mass index was 25.7 (4.1)kg/m(2). Level of 25(OH)D was 61.0 (27.2) nmol/L. There was a highly significant difference of 25(OH)D level across European countries (p < 0.0001). The lowest level of 25(OH)D was found in France [51.5 (26.1) nmol/L] and the highest in Spain [85.2 (33.3) nmol/L]. In the whole study population, the prevalence of 25(OH)D inadequacy was 79.6% and 32.1 % when considering cut-offs of 80 and 50 nmol/L, respectively and when considering patients aged less than 65 years, the prevalence reached 86% (cut-off of 80 nmol/L) and 45% (cutoff of 50 nmol/L). Conclusion: This study indicates a high prevalence of vitamin D [25(OH)D] inadequacy in European postmenopausal women. The prevalence could be even higher in some particular countries. A greater awareness of the importance of vitamin D inadequacy is needed to address this public health problem. [less ▲]

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See detailStrontium ranelate in the prevention of osteoporotic fractures
Reginster, Jean-Yves ULg; Malaise, Olivier ULg; Neuprez, Audrey et al

in International Journal of Clinical Practice (2007), 61(2), 324-328

Osteoporosis results from a decrease in bone strength yielding increased susceptibility to fractures. Hip and spine fractures are a major cause of morbidity and mortality in the elderly population. With ... [more ▼]

Osteoporosis results from a decrease in bone strength yielding increased susceptibility to fractures. Hip and spine fractures are a major cause of morbidity and mortality in the elderly population. With an increasingly ageing world population, early prevention of bone loss is essential for adequate control of this condition. Strontium ranelate (PROTELOS (R)), an oral drug for postmenopausal osteoporosis, has been reported to decrease bone resorption and to stimulate bone formation. The efficacy in reducing vertebral fractures, non-vertebral including hip fractures, and the safety of strontium ranelate has been initially demonstrated over 3 years in the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (TReatment Of Peripheral OSteoporosis) studies and confirmed recently over up to 5 years. A preplanned analysis of a sub-group of patients aged 80 years and over showed that, currently, strontium ranelate is the only antiosteoporotic agent to reduce vertebral and non-vertebral fractures in this age group. [less ▲]

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See detailIntermittent bisphosphonate therapy in postmenopausal osteoporosis - Progress to date
Reginster, Jean-Yves ULg; Malaise, Olivier ULg; Neuprez, A. et al

in Drugs & Aging (2007), 24(5), 351-359

Bisphosphonates are the most widely prescribed drugs in osteoporosis today. They have unequivocally shown their ability to reduce fracture rate at the spine (alendronic acid, risedronic acid, ibandronic ... [more ▼]

Bisphosphonates are the most widely prescribed drugs in osteoporosis today. They have unequivocally shown their ability to reduce fracture rate at the spine (alendronic acid, risedronic acid, ibandronic acid) and at the hip (alendronic acid and risedronic acid). However, their dosage and administration procedures and the adverse reactions induced by their oral intake are responsible for low adherence. Therefore, intermittent regimens have been developed. Weekly alendronic acid and risedronic acid provide similar benefits, in terms of bone mineral density (BMD) and changes in biochemical markers, as those seen with their daily formulations. Ibandronic acid has been shown to reduce vertebral fractures when given intermittently. Ibandronic acid given orally monthly and intravenously every 2 or 3 months provides increases in BMD similar to the daily formulation. Yearly intravenous infusions of zoledronic acid are currently being evaluated for their ability to reduce fractures. If the efficacy and safety of bisphosphonates given at administration intervals longer than weekly are confirmed, this might significantly improve patient adherence and long-term outcomes of bisphosphonate treatment in postmenopausal osteoporosis. [less ▲]

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See detailIntraveinous paracetamol: a review of efficacy and safety in therapeutic use
Malaise, Olivier ULg; Bruyère, Olivier ULg; Reginster, Jean-Yves ULg

in Future Neurology (2007), 2(6), 673-688

Paracetamol is well established as a leading nonprescription antipyretic analgesic drug and is available in oral, rectal or intravenous forms. However, except for oral paracetamol, there is a marked ... [more ▼]

Paracetamol is well established as a leading nonprescription antipyretic analgesic drug and is available in oral, rectal or intravenous forms. However, except for oral paracetamol, there is a marked discrepancy between the extent to which paracetamol is used and the available evidence for an analgesic effect in postoperative pain. This review mainly focuses on intravenous paracetamol. Its efficacy and safety are analyzed, as well as its use in therapeutics, alone or in combination. The morphine-sparing, additive and antihyperalgesia effects of intravenous paracetamol are also reviewed. The analyses are divided into several sections, comparing the efficacy of intravenous paracetamol with placebo, other forms of paracetamol or analgesic agents and analyzing its efficacy in multimodal therapy combined with NSAIDs or a morphinic agent. [less ▲]

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