Bio-Medical Materials and Engineering - Volume 20, issue 3-4

Authors: Paquet, Joseph | Maskali, Fathia | Poussier, Sylvain | Scala Bertola, Julien | Pinzano, Astrid | Grossin, Laurent | Netter, Patrick | Olivier, Pierre | Gillet, Pierre

Article Type: Research Article

Abstract: Aim: Assessing the activity of synovitis, which is characterized by an increase in cell metabolism, is important for the prediction of future articular destruction in clinical and preclinical studies. To evaluate the correlation between 18 F-FDG accumulation and arthritis pathology during its establishment, we used microPET to evaluted 18 F-FDG accumulation in vivo during rat Mycobacterium wall-induced knee arthritis. Methods: 18 F-FDG PET images of arthritic rats were acquired on days 1, 2, 3 and 7 after arthritis induction. The subjects (n=2/time) were subsequently subjected to macro-autoradiography, and 18 F-FDG accumulation was compared with histological findings. Results: 18 …F-FDG PET images depicted swollen joints, and 18 F-FDG accumulation increased with the progression of arthritis. Histologically, increased 18 F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. Conclusion: 18 F-FDG accumulation in arthritis reflects proliferating pannus and inflammatory activity enhanced by inflammatory cytokines. 18 F-FDG microPET should be effective for quantifying the inflammatory activity of arthritis and/or its therapeutic response. Show more

Keywords: Inflammation, synovitis, microPET, rat monoarthritis

DOI: 10.3233/BME-2010-0632

Citation: Bio-Medical Materials and Engineering, vol. 20, no. 3-4, pp. 195-202, 2010

Authors: Selvais, Charlotte | Dedieu, Stéphane | Hornebeck, William | Emonard, Hervé

Article Type: Research Article

Abstract: The low-density lipoprotein receptor-related protein (LRP-1) is a membrane receptor displaying both endocytic scavenging and signaling functions. In this review, we briefly present post-translational proteolytic processes targeting this receptor and speculate on their possible influence on LRP-1 biological functions.

Keywords: Endocytosis, low-density lipoprotein receptor-related protein, regulation, shedding, signaling

DOI: 10.3233/BME-2010-0633

Citation: Bio-Medical Materials and Engineering, vol. 20, no. 3-4, pp. 203-207, 2010

Authors: Hamade, Tala | Bianchi, Arnaud | Sebillaud, Sylvie | Netter, Patrick | Jouzeau, Jean-Yves | Cailotto, Frédéric

Article Type: Research Article

Abstract: The balance between extracellular inorganic phosphate (ePi) and extracellular inorganic pyrophosphate (ePPi) is controlled by four membrane proteins: the transporters ANK (exporting PPi outside the cells) and PiT-1 (importing ePi into the cells), and the enzymes PC-1 (generating ePPi from nucleotides) and Tissue Non-specific Alkaline Phosphatase (TNAP, hydrolyzing ePPi into ePi). TGF-β1 was shown to stimulate ANK and PC-1 expression in articular chondrocytes, and subsequent ePPi level, as well as to increase ePi uptake by inducing PiT-1 expression in a chondrogenic cell line. Thus, we investigated the ability of ePi to modulate the effect of TGF-β1 on the regulatory proteins …of the ePi/ePPi balance in chondrocytes. In the pathophysiological range of 0.01–1 mM, ePi was inactive by itself but potentiated the stimulatory effects of TGF-β1 on ANK, PC-1 or PiT-1 mRNA (RT-qPCR) and protein (Western blot) levels. PC-1 activity was also increased by TGF-β1 and further potentiated by ePi supplementation. TNAP mRNA and activity became undetectable in response to TGF-β1. These data suggest that ePi could increase ePPi level by changing the control of ANK and PC-1 expression by TGF-β1, further highlighting an adaptative regulation of the Pi/PPi balance to prevent basic calcium phosphate deposition into the joints. Show more

Keywords: Inorganic phosphate/pyrophosphate, TGF-β1, chondrocyte, ANK, PC-1

DOI: 10.3233/BME-2010-0634

Citation: Bio-Medical Materials and Engineering, vol. 20, no. 3-4, pp. 209-215, 2010

Authors: Ladhari, Nadia | Hemmerlé, Joseph | Haikel, Youssef | Voegel, Jean-Claude | Ball, Vincent

Article Type: Research Article

Abstract: Considering restrictive diabetes treatments, new insulin administration strategies constitute a huge medical challenge. This study aimed at developing a new support for insulin reservoirs, using polyelectrolyte multilayer films (PEM films), and thus studying this hormone release in a progressive manner. At first, insulin was loaded in (PDADMAC-PAA)n films, by immerging them for various periods of time (2, 14 and 24 h) in a solution containing this protein. Confocal laser scanning microscopy (CLSM) revealed that insulin-FITC could diffuse inside the film with a bigger concentration in the upper part of the film (after 2 and 14 h in contact with …the polypeptide solution), and then in the whole film (after 24 h) from a solution at pH=4.3 (below insulin's isolelectric point). Environmental scanning electron microscopy (ESEM) and CLSM showed that the film swells upon insulin loading. We finally investigated the insulin release by ATR–FTIR spectroscopy. It revealed that a loaded (PDADMAC-PAA)15 film, immerged in distilled water, showed no measurable insulin release. In contrast, a slow unloading was observed in the presence of a NaCl 0.15 M solution (salinity close to physiological serum). This study could open the route for a new way of insulin delivery. Show more

Keywords: Polyelectrolyte multilayer films, insulin, loading, unloading, drug delivery system, swelling

DOI: 10.3233/BME-2010-0635

Citation: Bio-Medical Materials and Engineering, vol. 20, no. 3-4, pp. 217-225, 2010

Authors: de Isla, N. | Charif, N. | Stoltz, J.F.

Article Type: Research Article

Abstract: The FoxO family of Forkhead transcription factors functions at the interface of tumor suppression, energy metabolism and organismal longevity. FoxO factors are key downstream targets of insulin, growth factor, nutrient and oxidative stress stimuli that coordinate a wide-range of cellular outputs. These transcription factors could participate in the regulation of different phenomena found in the osteoarthritis pathology, like apoptosis, chondrocyte proliferation, cell dedifferentiation or resistance to oxidative stress. Moreover, we found recently that FoxO transcription factors could be involved on Diacerhein mode of action, a drug that reduces the IL-1β deleterious effects on osteoarthritis cartilage through inhibition of the expression …of degrading enzymes. It could explain the downregulated proliferation and the increased p27 expression observed on human osteoarthritic chondrocytes in the presence of Diacerhein. Show more

Keywords: FoxO, osteoarthritis, Diacerhein, cartilage, apoptosis

DOI: 10.3233/BME-2010-0636

Citation: Bio-Medical Materials and Engineering, vol. 20, no. 3-4, pp. 227-233, 2010

Authors: Zille, Hervé | Paquet, Joseph | Henrionnet, Christel | Scala-Bertola, Julien | Leonard, Michèle | Six, Jean Luc | Deschamp, Frantz | Netter, Patrick | Vergès, José | Gillet, Pierre | Grossin, Laurent

Article Type: Research Article

Abstract: The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between …the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to assess the effects and localization of the nanocapsules in the knee joint. We did not observe significant modifications in the synovial membranes (weak hyperplasia) or patellae integrity after local administration of nanodevices into the rats. While we found some nanoparticles in the synovial membrane, none were detected in the patellae. Moreover, the histological observations for patellae were confirmed by radiosulfate intake, which depicted no decrease in proteoglycans biosynthesis in nanoparticles treated animals. Concerning the safety towards synovial membranes, we also had a look at the inflammatory response after injections of nanoparticles covered by amphiphilic HA or polyvinyl alcohol (PVA) by monitoring the mRNA expression levels of some specific early cytokines (IL-1β and TNF-α). Once again, no differences were observed between the control rats and the rats treated with nanoparticles. Considering these preliminary results obtained in healthy rats, we can establish that neither the amphiphilic HA-covered PLGA nanoparticles nor their degradation products induce major modifications of articular tissues functions, while injected into the knee of healthy rats. These results should be confirmed in OA or RA rat models, in order to confirm that nanoparticles do not worsen already altered (degenerative or inflamed) articular tissues. Once confirmed, such tuneable nanoparticles could be proposed as a safe drug delivery system for the treatment of articular disease, allowing a wide range of encapsulating molecules. Show more

Keywords: Intra-articular injection, hyaluronate, nanoparticles

DOI: 10.3233/BME-2010-0637

Citation: Bio-Medical Materials and Engineering, vol. 20, no. 3-4, pp. 235-242, 2010