Employees' Organizational Identification and Affective Organizational Commitment: An integrative approach
; ; et al
in PLoS ONE (2015), 10(4), 0123955
Although several studies have empirically supported the distinction between organizational identification (OI) and affective commitment (AC), there is still disagreement regarding how they are related ... [more ▼]
Although several studies have empirically supported the distinction between organizational identification (OI) and affective commitment (AC), there is still disagreement regarding how they are related. Precisely, little attention has been given to the direction of causality between these two constructs and as to why they have common antecedents and outcomes. This research was designed to fill these gaps. Using a cross-lagged panel design with two measurement times, Study 1 examined the directionality of the relationship between OI and AC, and showed that OI is positively related to temporal change in AC, confirming the antecedence of OI on AC. Using a cross-sectional design, Study 2 investigated the mediating role of OI in the relationship between three work experiences (i.e., perceived organizational support, leader-member exchange, and job autonomy) and AC, and found that OI partially mediates the influence of work experiences on AC. Finally, Study 3 examined longitudinally how OI and AC combine in the prediction of actual turnover, and showed that AC totally mediates the relationship between OI and turnover. Overall, these findings suggest that favorable work experiences operate via OI to increase employees' AC that, in turn, decreases employee turnover. [less ▲]Detailed reference viewed: 10 (0 ULg)
Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro-inflammatory properties
DE SENY, Dominique ; COBRAIVILLE, Gaël ; CHARLIER, Edith et al
in Plos One (2015)Detailed reference viewed: 41 (12 ULg)
High Resolution postontrast time of flight MR angiography of intracranial perforators at 7.0 Tesla
; ; et al
in PLoS ONE (2015)Detailed reference viewed: 18 (4 ULg)
Retirement age and the age of onset of Alzheimer’s disease: Results from the ICTUS study
Grotz, Catherine ; ; Bonsang, Eric et al
in PLoS ONE (2015), 10(2), 0115056Detailed reference viewed: 100 (35 ULg)
Time-varying respiratory system elastance: a physiological model for patients who are spontaneously breathing.
; ; et al
in PloS one (2015), 10(1), 0114847
BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no ... [more ▼]
BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (Edrs) model that can be used in spontaneously breathing patients to determine their respiratory mechanics. METHODS: A time-varying respiratory elastance model is developed with a negative elastic component (Edemand), to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS) and Neurally Adjusted Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. Edrs of every breathing cycle for each patient at different ventilation modes are presented for comparison. RESULTS: At the start of every breathing cycle initiated by patient, Edrs is < 0. This negativity is attributed from the Edemand due to a positive lung volume intake at through negative pressure in the lung compartment. The mapping of Edrs trajectories was able to give unique information to patients' breathing variability under different ventilation modes. The area under the curve of Edrs (AUCEdrs) for most patients is > 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS) severity indicator. CONCLUSION: The Edrs model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes. [less ▲]Detailed reference viewed: 20 (3 ULg)
Genome-Wide Analysis of In Vivo Binding of the Master Regulator DasR in Streptomyces coelicolor Identifies Novel Non-Canonical Targets
; ; et al
in PLoS ONE (2015)Detailed reference viewed: 30 (0 ULg)
Streptococcus pneumoniae GAPDH Is Released by Cell Lysis and Interacts with Peptidoglycan.
; Amoroso, Ana Maria ; et al
in PloS one (2015), 10(4), 0125377
Release of conserved cytoplasmic proteins is widely spread among Gram-positive and Gram-negative bacteria. Because these proteins display additional functions when located at the bacterial surface, they ... [more ▼]
Release of conserved cytoplasmic proteins is widely spread among Gram-positive and Gram-negative bacteria. Because these proteins display additional functions when located at the bacterial surface, they have been qualified as moonlighting proteins. The GAPDH is a glycolytic enzyme which plays an important role in the virulence processes of pathogenic microorganisms like bacterial invasion and host immune system modulation. However, GAPDH, like other moonlighting proteins, cannot be secreted through active secretion systems since they do not contain an N-terminal predicted signal peptide. In this work, we investigated the mechanism of GAPDH export and surface retention in Streptococcus pneumoniae, a major human pathogen. We addressed the role of the major autolysin LytA in the delivery process of GAPDH to the cell surface. Pneumococcal lysis is abolished in the DeltalytA mutant strain or when 1% choline chloride is added in the culture media. We showed that these conditions induce a marked reduction in the amount of surface-associated GAPDH. These data suggest that the presence of GAPDH at the surface of pneumococcal cells depends on the LytA-mediated lysis of a fraction of the cell population. Moreover, we demonstrated that pneumococcal GAPDH binds to the bacterial cell wall independently of the presence of the teichoic acids component, supporting peptidoglycan as a ligand to surface GAPDH. Finally, we showed that peptidoglycan-associated GAPDH recruits C1q from human serum but does not activate the complement pathway. [less ▲]Detailed reference viewed: 11 (3 ULg)
The alpha2,3-Sialyltransferase Encoded by Myxoma Virus Is a Virulence Factor that Contributes to Immunosuppression.
; ; et al
in PloS one (2015), 10(2), 0118806
Myxoma virus (MYXV) induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an alpha2,3-sialyltransferase through its M138L gene. In this study, we ... [more ▼]
Myxoma virus (MYXV) induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an alpha2,3-sialyltransferase through its M138L gene. In this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the M138L deficient strains are highly attenuated in vivo. Indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one rabbit inoculated with the M138L deficient strains survived the infection. In primary lesions, this resistance to the infection was associated with an increased ability of innate immune cells, mostly neutrophils, to migrate to the site of virus replication at 4 days post-infection. This was followed by the development of a better specific immune response against MYXV. Indeed, at day 9 post-infection, we observed an important proliferation of lymphocytes and an intense congestion of blood vessels in lymph nodes after M138L knockouts infection. Accordingly, in these rabbits, we observed an intense mononuclear cell infiltration throughout the dermis in primary lesions and higher titers of neutralizing antibodies. Finally, this adaptive immune response provided protection to these surviving rabbits against a challenge with the MYXV WT strain. Altogether, these results show that expression of the M138L gene contributes directly or indirectly to immune evasion by MYXV. In the future, these results could help us to better understand the pathogenesis of myxomatosis but also the importance of glycans in regulation of immune responses. [less ▲]Detailed reference viewed: 40 (11 ULg)
Elevated Plasma Soluble ST2 Is Associated with Heart Failure Symptoms and Outcome in Aortic Stenosis.
LANCELLOTTI, Patrizio ; DULGHERU, Raluca Elena ; et al
in PloS one (2015), 10(9), 0138940
B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is ... [more ▼]
B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74+/-13 years; 59 asymptomatic, 69%) with AS (<1.5 cm2) and preserved left ventricular ejection fraction who were followed-up for 26+/-16 months. Both BNP and sST2 were associated with NYHA class but sST2 (>23 ng/mL, AUC = 0.68, p<0.01) was more accurate to identify asymptomatic patients or those who developed symptoms during follow-up. sST2 was independently related to left atrial index (p<0.0001) and aortic valve area (p = 0.004; model R2 = 0.32). A modest correlation was found with BNP (r = 0.4, p<0.01). During follow-up, 29 asymptomatic patients (34%) developed heart failure symptoms. With multivariable analysis, peak aortic jet velocity (HR = 2.7, p = 0.007) and sST2 level (HR = 1.04, p = 0.03) were independent predictors of cardiovascular events. In AS, sST2 levels could provide complementary information regarding symptomatic status, new onset heart failure symptoms and outcome. It might become a promising biomarker in these patients. [less ▲]Detailed reference viewed: 42 (10 ULg)
Identification of the neutralizing epitopes of Merkel cell polyomavirus major capsid protein within the BC and EF surface loops.
; Nicol, Jérôme ; et al
in PloS one (2015), 10(3), 0121751
Merkel cell polyomavirus (MCPyV) is the first polyomavirus clearly associated with a human cancer, i.e. the Merkel cell carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce a robust ... [more ▼]
Merkel cell polyomavirus (MCPyV) is the first polyomavirus clearly associated with a human cancer, i.e. the Merkel cell carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce a robust polyclonal antibody response against the major capsid protein (VP1). However, the polyomavirus VP1 capsid protein epitopes have not been identified to date. The aim of this study was to identify the neutralizing epitopes of the MCPyV capsid. For this goal, four VP1 mutants were generated by insertional mutagenesis in the BC, DE, EF and HI loops between amino acids 88-89, 150-151, 189-190, and 296-297, respectively. The reactivity of these mutants and wild-type VLPs was then investigated with anti-VP1 monoclonal antibodies and anti-MCPyV positive human sera. The findings together suggest that immunodominant conformational neutralizing epitopes are present at the surface of the MCPyV VLPs and are clustered within BC and EF loops. [less ▲]Detailed reference viewed: 1 (0 ULg)
The aerodynamic cost of head morphology in bats: maybe not as bad as it seems
; ; et al
in PLoS ONE (2015), 10(3), 0118545
At first sight, echolocating bats face a difficult trade-off. As flying animals, they would benefit from a streamlined geometric shape to reduce aerodynamic drag and increase flight efficiency. However ... [more ▼]
At first sight, echolocating bats face a difficult trade-off. As flying animals, they would benefit from a streamlined geometric shape to reduce aerodynamic drag and increase flight efficiency. However, as echolocating animals, their pinnae generate the acoustic cues necessary for navigation and foraging. Moreover, species emitting sound through their nostrils often feature elaborate noseleaves that help in focussing the emitted echolocation pulses. Both pinnae and noseleaves reduce the streamlined character of a bat’s morphology. It is generally assumed that by compromising the streamlined charactered of the geometry, the head morphology generates substantial drag, thereby reducing flight efficiency. In contrast, it has also been suggested that the pinnae of bats generate lift forces counteracting the detrimental effect of the increased drag. However, very little data exist on the aerodynamic properties of bat pinnae and noseleaves. In this work, the aerodynamic forces generated by the heads of seven species of bats, including noseleaved bats, are measured by testing detailed 3D models in a wind tunnel. Models of Myotis daubentonii, Macrophyllum macrophyllum, Micronycteris microtis, Eptesicus fuscus, Rhinolophus formosae, Rhinolophus rouxi and Phyllostomus discolor are tested. The results confirm that non-streamlined facial morphologies yield considerable drag forces but also generate substantial lift. The net effect is a slight increase in the lift-to-drag ratio. Therefore, there is no evidence of high aerodynamic costs associated with the morphology of bat heads [less ▲]Detailed reference viewed: 52 (18 ULg)
A Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) - Discoidin Domain Receptor 1 Axis Regulates Collagen-Induced Apoptosis in Breast Cancer Cells.
; Bourgot, Isabelle ; Hennuy, Benoît et al
in PloS one (2015), 10(3), 0116006
During tumour dissemination, invading breast carcinoma cells become confronted with a reactive stroma, a type I collagen-rich environment endowed with anti-proliferative and pro-apoptotic properties. To ... [more ▼]
During tumour dissemination, invading breast carcinoma cells become confronted with a reactive stroma, a type I collagen-rich environment endowed with anti-proliferative and pro-apoptotic properties. To develop metastatic capabilities, tumour cells must acquire the capacity to cope with this novel microenvironment. How cells interact with and respond to their microenvironment during cancer dissemination remains poorly understood. To address the impact of type I collagen on the fate of tumour cells, human breast carcinoma MCF-7 cells were cultured within three-dimensional type I collagen gels (3D COL1). Using this experimental model, we have previously demonstrated that membrane type-1 matrix metalloproteinase (MT1-MMP), a proteinase overexpressed in many aggressive tumours, promotes tumour progression by circumventing the collagen-induced up-regulation of BIK, a pro-apoptotic tumour suppressor, and hence apoptosis. Here we performed a transcriptomic analysis to decipher the molecular mechanisms regulating 3D COL1-induced apoptosis in human breast cancer cells. Control and MT1-MMP expressing MCF-7 cells were cultured on two-dimensional plastic plates or within 3D COL1 and a global transcriptional time-course analysis was performed. Shifting the cells from plastic plates to 3D COL1 activated a complex reprogramming of genes implicated in various biological processes. Bioinformatic analysis revealed a 3D COL1-mediated alteration of key cellular functions including apoptosis, cell proliferation, RNA processing and cytoskeleton remodelling. By using a panel of pharmacological inhibitors, we identified discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase specifically activated by collagen, as the initiator of 3D COL1-induced apoptosis. Our data support the concept that MT1-MMP contributes to the inactivation of the DDR1-BIK signalling axis through the cleavage of collagen fibres and/or the alteration of DDR1 receptor signalling unit, without triggering a drastic remodelling of the transcriptome of MCF-7 cells. [less ▲]Detailed reference viewed: 45 (6 ULg)
Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs.
; ; et al
in PloS one (2015), 10(6), 0130227
To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells ... [more ▼]
To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds) becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells) in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial 'design of experiments' approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid) and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology. [less ▲]Detailed reference viewed: 47 (3 ULg)
Non Digestible Oligosaccharides Modulate the Gut Microbiota to Control the Development of Leukemia and Associated Cachexia in Mice.
; ; et al
in PloS one (2015), 10(6), 0131009
We tested the hypothesis that changing the gut microbiota using pectic oligosaccharides (POS) or inulin (INU) differently modulates the progression of leukemia and related metabolic disorders. Mice were ... [more ▼]
We tested the hypothesis that changing the gut microbiota using pectic oligosaccharides (POS) or inulin (INU) differently modulates the progression of leukemia and related metabolic disorders. Mice were transplanted with Bcr-Abl-transfected proB lymphocytes mimicking leukemia and received either POS or INU in their diet (5%) for 2 weeks. Combination of pyrosequencing, PCR-DGGE and qPCR analyses of the 16S rRNA gene revealed that POS decreased microbial diversity and richness of caecal microbiota whereas it increased Bifidobacterium spp., Roseburia spp. and Bacteroides spp. (affecting specifically B. dorei) to a higher extent than INU. INU supplementation increased the portal SCFA propionate and butyrate, and decreased cancer cell invasion in the liver. POS treatment did not affect hepatic cancer cell invasion, but was more efficient than INU to decrease the metabolic alterations. Indeed, POS better than INU delayed anorexia linked to cancer progression. In addition, POS treatment increased acetate in the caecal content, changed the fatty acid profile inside adipose tissue and counteracted the induction of markers controlling beta-oxidation, thereby hampering fat mass loss. Non digestible carbohydrates with prebiotic properties may constitute a new nutritional strategy to modulate gut microbiota with positive consequences on cancer progression and associated cachexia. [less ▲]Detailed reference viewed: 163 (7 ULg)
Effects of Moderate Amounts of Barley in Late Pregnancy on Growth, Glucose, Metabolism and Osteoarticular Sataus of Pre-Weaning Horses
; ; Mendoza García, Luis et al
in PLoS ONE (2015)Detailed reference viewed: 36 (8 ULg)
Zebrafish bone and general physiology are differently affected by hormones or changes in gravity.
Aceto, Jessica ; ; Marée, Raphaël et al
in PLoS ONE (2015), 10(6), 1-42
Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire ... [more ▼]
Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. [less ▲]Detailed reference viewed: 233 (21 ULg)
Quality of Antimicrobial Products Used in Striped Catfish (Pangasianodon hypophthalmus) Aquaculture in Vietnam.
; ; Scippo, Marie-Louise et al
in PLoS ONE (2015), 10(4): e0124267. doi:10.1371/journal.pone.0124267Detailed reference viewed: 29 (9 ULg)
What do Pneumocystis organisms tell us about the phylogeography of their hosts? The case of the woodmouse Apodemus sylvaticus in continental Europe and western Mediterranean islands
; ; Michaux, Johan et al
in PLoS ONE (2015), DOI:10.1371
Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the ... [more ▼]
Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the presence and genetic diversity of Pneumocystis organisms was investigated in 203 lung samples from woodmice (Apodemus sylvaticus) collected on western continental Europe and Mediterranean islands. The presence of Pneumocystis DNA was assessed by nested PCR at both large and small mitochondrial subunit (mtLSU and mtSSU) rRNA loci. Direct sequencing of nested PCR products demonstrated a very high variability among woodmouse-derived Pneumocystis organisms with a total number of 30 distinct combined mtLSU and mtSSU sequence types. However, the genetic divergence among these sequence types was very low (up to 3.87%) and the presence of several Pneumocystis species within Apodemus sylvaticus was considered unlikely. The analysis of the genetic structure of woodmouse-derived Pneumocystis revealed two distinct groups. The first one comprised Pneumocystis from woodmice collected in continental Spain, France and Balearic islands. The second one included Pneumocystis from woodmice collected in continental Italy, Corsica and Sicily. These two genetic groups were in accordance with the two lineages currently described within the host species Apodemus sylvaticus. Pneumocystis organisms are emerging as powerful tools for phylogeographic studies in mammals [less ▲]Detailed reference viewed: 66 (5 ULg)
Layman versus Professional Musician: Who Makes the Better Judge?
Larrouy, Pauline ; Magis, David ; et al
in PLoS ONE (2015)
The increasing number of casting shows and talent contests in the media over the past years suggests a public interest in rating the quality of vocal performances. In many of these formats, laymen ... [more ▼]
The increasing number of casting shows and talent contests in the media over the past years suggests a public interest in rating the quality of vocal performances. In many of these formats, laymen alongside music experts act as judges. Whereas experts' judgments are considered objective and reliable when it comes to evaluating singing voice, little is known about laymen’s ability to evaluate peers. On the one hand, layman listeners–who by definition did not have any formal training or regular musical practice–are known to have internalized the musical rules on which singing accuracy is based. On the other hand, lay- man listeners’ judgment of their own vocal skills is highly inaccurate. Also, when compared with that of music experts, their level of competence in pitch perception has proven limited. The present study investigates laypersons' ability to objectively evaluate melodies per- formed by untrained singers. For this purpose, laymen listeners were asked to judge sung melodies. The results were compared with those of music experts who had performed the same task in a previous study. Interestingly, the findings show a high objectivity and reliabil- ity in layman listeners. Whereas both the laymen's and experts' definition of pitch accuracy overlap, differences regarding the musical criteria employed in the rating task were evident. The findings suggest that the effect of expertise is circumscribed and limited and supports the view that laypersons make trustworthy judges when evaluating the pitch accuracy of untrained singers. [less ▲]Detailed reference viewed: 60 (12 ULg)
Carnosol Inhibits Pro-Inflammatory and Catabolic Mediators of Cartilage Breakdown in Human Osteoarthritic Chondrocytes and Mediates Cross-Talk between Subchondral Bone Osteoblasts and Chondrocytes.
Sanchez, Christelle ; ; et al
in PloS one (2015), 10(8), 0136118
AIM: The aim of this work was to evaluate the effects of carnosol, a rosemary polyphenol, on pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes and via bone-cartilage ... [more ▼]
AIM: The aim of this work was to evaluate the effects of carnosol, a rosemary polyphenol, on pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes and via bone-cartilage crosstalk. MATERIALS AND METHODS: Osteoarthritic (OA) human chondrocytes were cultured in alginate beads for 4 days in presence or absence of carnosol (6 nM to 9 muM). The production of aggrecan, matrix metalloproteinase (MMP)-3, tissue inhibitor of metalloproteinase (TIMP)-1, interleukin (IL)-6 and nitric oxide (NO) and the expression of type II collagen and ADAMTS-4 and -5 were analyzed. Human osteoblasts from sclerotic (SC) or non-sclerotic (NSC) subchondral bone were cultured for 3 days in presence or absence of carnosol before co-culture with chondrocytes. Chondrocyte gene expression was analyzed after 4 days of co-culture. RESULTS: In chondrocytes, type II collagen expression was significantly enhanced in the presence of 3 muM carnosol (p = 0.008). MMP-3, IL-6, NO production and ADAMTS-4 expression were down-regulated in a concentration-dependent manner by carnosol (p<0.01). TIMP-1 production was slightly increased at 3 muM (p = 0.02) and ADAMTS-5 expression was decreased from 0.2 to 9 muM carnosol (p<0.05). IL-6 and PGE2 production was reduced in the presence of carnosol in both SC and NSC osteoblasts while alkaline phosphatase activity was not changed. In co-culture experiments preincubation of NSC and SC osteoblasts wih carnosol resulted in similar effects to incubation with anti-IL-6 antibody, namely a significant increase in aggrecan and decrease in MMP-3, ADAMTS-4 and -5 gene expression by chondrocytes. CONCLUSIONS: Carnosol showed potent inhibition of pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes. Inhibition of matrix degradation and enhancement of formation was observed in chondrocytes cocultured with subchondral osteoblasts preincubated with carnosol indicating a cross-talk between these two cellular compartments, potentially mediated via inhibition of IL-6 in osteoblasts as similar results were obtained with anti-IL-6 antibody. [less ▲]Detailed reference viewed: 20 (3 ULg)