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Brij Bhushan Mehta, Anil Tiwari, Saniya Sharma, Ashu Shukla, Maryada Sharma, Rakesh K Vasishta, Ramesh K Sen, Aman Sharma, Manni Luthra-Guptasarma
Tenascin-C (TN-C) levels are elevated in the synovial tissue and fluid, as well as cartilage of rheumatoid arthritis (RA) patients. In addition, the presence of TN-C fragments has also been documented in arthritic cartilage. We have previously shown that a single chain variable fragment antibody (TN64), directed against the fibronectin type III repeats 1-5 (TNfnIII 1-5) of TN-C, effectively inhibits fibrotic pathology. Given that fibrosis results from chronic inflammation, and the fact that increased levels of TN-C in the synovial fluid of patients with RA contributes to synovial inflammation and joint destruction, we aimed to investigate the role of TNfnIII 1-5 region of TN-C in RA pathogenesis...
March 9, 2018: International Immunopharmacology
Priyam Jani, Chao Liu, Hua Zhang, Khaled Younes, M Douglas Benson, Chunlin Qin
OBJECTIVE: The bone morphogenetic proteins (BMPs) play crucial roles in tooth development. However, several BMPs retain expression in the dentin of the fully patterned and differentiated tooth. We hypothesized that BMP signaling therefore plays a role in the function of the differentiated odontoblast, the job of which is to lay down and mineralize the dentin matrix. DESIGN: We generated mice deficient in Bmp2 and 4 using a dentin matrix protein 1 (Dmp1) promoter-driven cre recombinase that was expressed in differentiated odontoblasts...
February 7, 2018: Archives of Oral Biology
Orestis G Andriotis, Sylvia Desissaire, Philipp J Thurner
Tissue hydration is well known to influence tissue mechanics and can be tuned via osmotic pressure. Collagen fibrils are nature's nanoscale building blocks to achieve biomechanical function in a broad range of biological tissues and across many species. Intrafibrillar covalent cross-links have long been thought to play pivotal role for collagen fibril elasticity, but predominantly at large, far from physiological, strains. Performing nanotensile experiments of collagen fibrils at varying hydration levels by adjusting osmotic pressure in situ during atomic force microscopy experiments, we show the power the intrafibrillar non-covalent interactions have for defining collagen fibril tensile elasticity at low fibril strains...
March 12, 2018: ACS Nano
Nicole Jedrusik, Christoph Meyen, Günter Finkenzeller, G Björn Stark, Stephan Meskath, Simon Daniel Schulz, Thorsten Steinberg, Philipp Eberwein, Sandra Strassburg, Pascal Tomakidi
Regarding tissue regeneration, mechanics of biomaterials gains progressive importance. Therefore, this study reports on in situ crosslinked electrospun gelatin nonwoven mats (NWMs) whose distinct modulus of elasticity (ME) promotes epithelial tissue formation in a graded manner. NWMs, comprising fiber diameters in various distributions, yield an ME of about 2.1, 3.2, and 10.9 kPa. A two-step approach of preclinical in vitro validation identifies the elasticity of 3.2 kPa as superior to the other, regarding the histogenetic epithelial outcome...
March 12, 2018: Advanced Healthcare Materials
Bin Sheng, Youchao Yuan, Xiangyang Liu, Yi Zhang, Hongzhe Liu, Xiongjie Shen, Bin Liu, Lei Chang
Dysfunction of cartilaginous endplates (CEP) is an important etiologic aspect of intervertebral disc degeneration (IDD) because the endplate has nutritional and biomechanical functions in maintaining proper disc health. In this study, we investigated the regulatory effects of estrogen on degenerated human CEP cells and the involvement of miR-221 in these effects. Normal and degenerated human CEP tissues were collected from patients with idiopathic scoliosis and IDD, respectively. CEP cells were isolated from these tissues...
February 26, 2018: Acta Biochimica et Biophysica Sinica
Ana Valero-Jiménez, Joaquín Zúñiga, José Cisneros, Carina Becerril, Alfonso Salgado, Marco Checa, Ivette Buendía-Roldán, Criselda Mendoza-Milla, Miguel Gaxiola, Annie Pardo, Moisés Selman
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by epithelial cell activation, expansion of the fibroblast population and excessive extracellular matrix accumulation. The mechanisms are incompletely understood but evidence indicates that the deregulation of several proteases contributes to its pathogenesis. Transmembrane protease serine 4 (TMPRSS4) is a novel type II transmembrane serine protease that may promote migration and facilitate epithelial to mesenchymal transition (EMT), two critical processes in the pathogenesis of IPF...
2018: PloS One
Jahidur Rashid, Kamrun Nahar, Snehal Raut, Ali Keshavarz, Fakhrul Ahsan
We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long acting nitric oxide donorboth loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC)in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified- and CAR-modified-liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia induced PAH rats...
March 12, 2018: Molecular Pharmaceutics
Wen Yin, Xing Li, Yannan Zhao, Jun Tan, Shuyu Wu, Yudong Cao, Juan Li, Hecheng Zhu, Weidong Liu, Guihua Tang, Li Meng, Lei Wang, Bin Zhu, Gousiyi Wang, Meizuo Zhong, Xingdong Liu, Dan Xie, Bing Chen, Caiping Ren, Zhifeng Xiao, Xingjun Jiang, Jianwu Dai
Treatment of spinal cord injury (SCI) remains a clinical challenge worldwide because of the complicated inhibitory microenvironment formed post-injury, reduced axonal regenerative ability of spinal cord neurons, and scarcity of endogenous neurogenesis within the lesion center. Taxol, in addition to stabilizing microtubules, has shown potential for decreasing axonal degeneration and reducing scar formation after SCI in rodents. In this study, we further verified the therapeutic effects and clinical potential of Taxol on restriction of scar formation and promotion of neuronal regeneration and functional recovery after severe spinal cord transection in a large animal (canine) model...
March 12, 2018: Biomaterials Science
Min Jiang, Qiang Lyu, Yun-Gang Bai, Huan Liu, Jing Yang, Jiu-Hua Cheng, Ming Zheng, Jin Ma
Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated microgravity-induced basilar and femoral arterial remodelling...
March 11, 2018: Canadian Journal of Physiology and Pharmacology
M Gasser, M H Frank, A M Waaga-Gasser
Critical chronic ischemia in patients with underlying arterial occlusive disease requires vascular reconstructive surgery. The limited supply of suitable small-diameter autologous vascular grafts in many patients and obvious disadvantages of synthetic bypass material demand the development of clinically usable tissue-engineered blood vessel substitutes. Despite substantial progress in the field over the last two decades, their implementation into the clinical routine has been challenging. The limited replicative life span of human adult vascular cells and their slow rate of collagenous matrix production in vitro have posed important problems in the development of mechanically robust and biologically functional engineered grafts...
February 2018: Gefässchirurgie: Zeitschrift Für Vaskuläre und Endovaskuläre Chirurgie
Tongliang Ma, Decai Zhu, Duoxue Chen, Qiaoyun Zhang, Huifang Dong, Wenwu Wu, Huihe Lu, Guangfu Wu
BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts...
March 12, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Mao Li, Xi Chen, Jinku Yan, Long Zhou, Yifan Wang, Fan He, Jun Lin, Caihong Zhu, Guoqing Pan, Jia Yu, Ming Pei, Huilin Yang, Tao Liu
Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration because of the promotion effect on osteogenesis in mesenchymal stem cells (MSCs). However, bone regeneration is also influenced by bone resorption and little is known about the effect of cell-derived ECM on osteoclast differentiation. In this study, ECM was deposited by MSCs and, after decellularization, the effect of ECM on osteoclastogenesis of bone marrow monocytes (BMMs) was investigated in comparison to standard tissue culture polystyrene...
March 8, 2018: Acta Biomaterialia
Hyun Ju Lim, Zara Khan, Xi Lu, T Hiran Perera, Thomas S Wilems, Krishna T Ravivarapu, Laura A Smith Callahan
Balancing enhancement of neurite extension against loss of matrix support in synthetic hydrogels containing proteolytically degradable and bioactive signaling peptides to optimize tissue formation is difficult. Using a systematic approach, polyethylene glycol hydrogels containing concurrent continuous concentration gradients of the laminin derived bioactive signaling peptide, Ile-Lys-Val-Ala-Val (IKVAV), and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ, were fabricated and characterized...
March 8, 2018: Acta Biomaterialia
Xiaobin Huang, Janine N Post, Leilei Zhong, Jeroen Leijten, Staffan Larsson, Marcel Karperien, André Struglics
OBJECTIVE: To explore the involvement of the WNT and BMP antagonists Dickkopf-related protein 1 (DKK1), Frizzled-related protein (FRZB) and Gremlin 1 (GREM1) in knee injury and osteoarthritis (OA). DESIGN: The antagonists were immunoassayed in synovial fluid from a cross-sectional cohort of 9 knee healthy reference subjects, patients with recent (0-77 days, n=158) or old (1-37 years, n=50) knee injuries, and OA (n=22). Cartilage (ARGS-aggrecan, cartilage oligomeric matrix protein and C2C type II collagen) and other biomarkers were assessed in synovial fluid in a subset of samples...
March 8, 2018: Osteoarthritis and Cartilage
Kohei Omachi, Misato Kamura, Keisuke Teramoto, Haruka Kojima, Tsubasa Yokota, Shota Kaseda, Jun Kuwazuru, Ryosuke Fukuda, Kosuke Koyama, Shingo Matsuyama, Keishi Motomura, Tsuyoshi Shuto, Mary Ann Suico, Hirofumi Kai
Alport syndrome is a hereditary glomerular disease caused by mutation in type IV collagen α3-α5 chains (α3-α5(IV)), which disrupts trimerization, leading to glomerular basement membrane degeneration. Correcting the trimerization of α3/α4/α5 chain is a feasible therapeutic approach, but is hindered by lack of information on the regulation of intracellular α(IV) chain and the absence of high-throughput screening (HTS) platforms to assess α345(IV) trimer formation. Here, we developed sets of split NanoLuc-fusion α345(IV) proteins to monitor α345(IV) trimerization of wild-type and clinically associated mutant α5(IV)...
February 21, 2018: Cell Chemical Biology
Gabriela Recalde, Tamara Moreno-Sosa, Florencia Yudica, Cristian A Quintero, Belén Sanchez, Graciela A Jahn, Alexis M Kalergis, Juan Pablo Mackern-Oberti
In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an anti- inflammatory and immunosuppressive effect...
March 8, 2018: Autoimmunity Reviews
Vasundhara Kain, Kevin A Ingle, Janusz Kabarowski, Stephen Barnes, Nita A Limdi, Sumanth D Prabhu, Ganesh V Halade
12/15 lipoxygenase (LOX) directs inflammation and lipid remodeling. However, the role of 12/15LOX in post-myocardial infarction (MI) left ventricular remodeling is unclear. To determine the role of 12/15LOX, 8-12 week-old C57BL/6 J wild-type (WT; n = 93) and 12/15LOX-/- (n = 97) mice were subjected to permanent coronary artery ligation and monitored at day (d)1 and d5 post-operatively. Post-MI d28 survival was measured in male and female mice. No-MI surgery mice were maintained as d0 naïve controls...
March 8, 2018: Journal of Molecular and Cellular Cardiology
Jack P Carson, Grant A Ramm, Mark W Robinson, Donald P McManus, Geoffrey N Gobert
Hepatic fibrosis is a common pathology in various liver diseases. Hepatic stellate cells (HSCs) are the main cell type responsible for collagen deposition and fibrosis formation in the liver. Schistosomiasis is characterised by granulomatous fibrosis around parasite eggs trapped within the liver and other host tissues. This response is facilitated by the recruitment of immune cells and the activation of HSCs. The interactions between HSCs and schistosome eggs are complex and diverse, and a better understanding of these interactions could lead to improved resolution of fibrotic liver disease, including that associated with schistosomiasis...
March 8, 2018: Trends in Parasitology
Yılmaz Eren, Oktay Adanır, Yaşar Mahsut Dinçel, Erdinç Genç, Yunus Ziya Arslan, Aysel Çağlar
OBJECTIVES: This study aims to compare the histopathological and biomechanical effects of low molecular weight heparin (LMWH) and rivaroxaban, which are frequently used in orthopedic surgery for thromboembolic prophylaxis, on rat Achilles tendon healing. MATERIALS AND METHODS: In the study, 36 adult, male Sprague Dawley rats weighing between 300 g and 400 g were used. Three groups were formed including 12 rats in each. Achilles tendons of all rats were cut and repaired...
April 2018: Eklem Hastalıkları Ve Cerrahisi, Joint Diseases & related Surgery
Pablo J Sáez, Lucie Barbier, Rafaele Attia, Hawa-Racine Thiam, Matthieu Piel, Pablo Vargas
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21...
2018: Methods in Molecular Biology
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