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Cartilage development

Onoufrios Tsavaris, Panagiota Economopoulou, Ioannis Kotsantis, Lazaros Reppas, Chrysanthi Avgerinou, Nikolaos Spathas, Maria Prevezanou, Amanda Psyrri
Chondrosarcoma is a rare malignancy characterized by the production of cartilage matrix, displaying heterogeneous histopathology and clinical behavior. Due to lack of effective treatment for advanced disease, the clinical management of metastatic chondrosarcoma is exceptionally challenging. Chondrosarcomas harbor molecular abnormalities, such as overexpression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, which are required for cancer development, progression, and metastasis. Pazopanib is a potent and selective multitargeted tyrosine kinase inhibitor, which co-inhibits stem cell growth factor receptor (c-KIT), fibroblast growth factor receptor (FGFR), PDGFR, and vascular endothelial growth factor receptor (VEGFR) and has demonstrated clinical activity in patients with advanced previously treated soft tissue sarcoma...
2018: Frontiers in Oncology
Yuan-Jun Xia, Hong Xia, Ling Chen, Qing-Shui Ying, Xiang Yu, Li-Hua Li, Jian-Hua Wang, Ying Zhang
Bone morphogenetic protein-2 (BMP-2) serves an important role in the development of bone and cartilage. However, administration of BMP-2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP-2 by carriers has been proven necessary to improve the osteogenesis effect of BMP-2. The present study constructed a novel drug delivery system using dextran sulfate (DS)-chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP-2)...
April 2018: Experimental and Therapeutic Medicine
Brooke McClarren, Ronke Olabisi
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into any mesenchymal tissue, including bone, cartilage, muscle, and fat. MSC differentiation can be influenced by a variety of stimuli, including environmental and mechanical stimulation, scaffold physical properties, or applied loads. Numerous studies have evaluated the effects of vibration or cyclic tensile strain on MSCs towards developing a mechanically based method of differentiation, but there is no consensus between studies and each investigation uses different culture conditions, which also influence MSC fate...
2018: International Journal of Biomaterials
Virginia Piombo, Katja Jochmann, Daniel Hoffmann, Manuela Wuelling, Andrea Vortkamp
Multiple osteochondromas (MO) syndrome is a dominant autosomal bone disorder characterized by the formation of cartilage-capped bony outgrowths that develop at the juxtaposition of the growth plate of endochondral bones. MO has been linked to mutations in either EXT1 or EXT2, two glycosyltransferases required for the synthesis of heparan sulfate (HS). The establishment of mouse mutants demonstrated that a clonal, homozygous loss of Ext1 in a wild type background leads to the development of osteochondromas. Here we investigate mechanisms that might contribute to the variation in the severity of the disease observed in human patients...
March 12, 2018: Bone
Andrew J Olsen, Priya Katyal, Jennifer S Haghpanah, Matthew B Kubilius, Ruipeng Li, Nicole L Schnabel, Sean C O'Neill, Yao Wang, Min Dai, Navjot Singh, Raymond S Tu, Jin Kim Montclare
Recombinant methods have been used to engineer artificial protein triblock polymers comprised of two different self-assembling domains (SADs) bearing one elastin (E) flanked by two cartilage oligomeric matrix protein coiled-coil (C) domains to generate CEC. To understand how the two C domains improve small molecule recognition and the mechanical integrity of CEC, we have constructed CL44AECL44A, which bears an impaired CL44A domain that is unstructured as a negative control. The CEC triblock polymer demonstrates increased small molecule binding and ideal elastic behavior for hydrogel formation...
March 15, 2018: Biomacromolecules
Carrie K Hui Mingalone, Zhiyi Liu, Judith M Hollander, Kirsten D Garvey, Averi L Gibson, Rose E Banks, Ming Zhang, Timothy E McAlindon, Heber C Nielsen, Irene Georgakoudi, Li Zeng
Osteoarthritis (OA) is a leading cause of chronic disability whose mechanism of pathogenesis is largely elusive. Local inflammation is thought to play a key role in OA progression, especially in injury-associated OA. While multiple inflammatory cytokines are detected, the timing and extent of overall inflammatory activities in early OA and the manner by which joint inflammation correlates with cartilage structural damage are still unclear. We induced OA via destabilization of the medial meniscus (DMM) in NFκB luciferase reporter mice, whose bioluminescent signal reflects the activity of NFκB, a central mediator of inflammation...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Joshua J Heerey, Joanne L Kemp, Andrea B Mosler, Denise M Jones, Tania Pizzari, Richard B Souza, Kay M Crossley
BACKGROUND: Intra-articular hip pathologies are thought to be associated with the development of hip and groin pain. A better understanding of the relationship between symptoms and imaging findings may improve the management of individuals with intra-articular hip pathologies. OBJECTIVE: To undertake a systematic review and meta-analysis to determine the prevalence of intra-articular hip pathologies in individuals with and without pain. METHODS: Seven electronic databases were searched in February 2017 for studies investigating the prevalence of intra-articular hip pathologies using MRI, MRA or CT...
March 14, 2018: British Journal of Sports Medicine
Kai Wang, Dongmei Zhang, Yan Liu, Xuan Wang, Jiantong Zhao, Tingting Sun, Tingting Jin, Baoli Li, Janak L Pathak
BACKGROUND: Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. METHODS: CIA was developed in Sprague-Dawley (S...
March 14, 2018: Arthritis Research & Therapy
Jaime L Bernstein, Benjamin P Cohen, Alexandra Lin, Alice Harper, Lawrence J Bonassar, Jason A Spector
PURPOSE: The significant shortcomings associated with current autologous reconstructive options for auricular deformities have inspired great interest in a tissue engineering solution. A major obstacle in the engineering of human auricular cartilage is the availability of sufficient autologous human chondrocytes. A clinically obtainable amount of auricular cartilage tissue (ie, 1 g) only yields approximately 10 million cells, where 25 times this amount is needed for the fabrication of a full-scale pediatric ear...
March 13, 2018: Annals of Plastic Surgery
Jason Talmadge, Robin High, William Wesley Heckman
IMPORTANCE: Spreader grafts are commonly used for nasal valve stenosis. There is debate among practitioners regarding the optimal approach for spreader graft placement. OBJECTIVE: This study aimed to determine whether an endonasal spreader graft placement leads to equivalent postoperative outcomes using a standardized nasal obstruction symptom score and whether there is a significant difference in operative time between the 2 approaches. DESIGN: A retrospective review of functional rhinoplasties by a single facial plastic surgeon over a 2-year period was conducted...
March 13, 2018: Annals of Plastic Surgery
Yeri Alice Rim, Yoojun Nam, Narae Park, Hyerin Jung, Yeonsue Jang, Jennifer Lee, Ji Hyeon Ju
Scientists have tried to reprogram various origins of primary cells into human induced pluripotent stem cells (hiPSCs). Every somatic cell can theoretically become a hiPSC and give rise to targeted cells of the human body. However, there have been debates on the controversy about the differentiation propensity according to the origin of primary cells. We reprogrammed hiPSCs from four different types of primary cells such as dermal fibroblasts (DF, n = 3), peripheral blood mononuclear cells (PBMC, n = 3), cord blood mononuclear cells (CBMC, n = 3), and osteoarthritis fibroblast-like synoviocytes (OAFLS, n = 3)...
2018: Stem Cells International
Silvia Lopa, Carlotta Mondadori, Valerio Luca Mainardi, Giuseppe Talò, Marco Costantini, Christian Candrian, Wojciech Święszkowski, Matteo Moretti
Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells...
2018: Stem Cells International
Hongsik Cho, Byoung Ju Kim, Sang-Hyug Park, Karen A Hasty, Byoung-Hyun Min
Background: Early stage osteoarthritis (OA) is clinically asymptomatic due to the avascular and the aneural nature of the cartilage tissue. Nevertheless, early detection of cartilage tissue is critical in order to impede the progression of OA. Hence, in order to develop effective preventive therapy for OA, diagnosis in the early stages is necessary. Methods: To achieve this goal, we have developed targeted, fluorescent nanosomes conjugated with monoclonal anti-type II collagen antibodies (MabCII) for diagnosis of early OA...
2018: International Journal of Nanomedicine
Ji Eun Kim, Da-Hyun Song, Soo Hyun Kim, Youngmee Jung, Sang Jun Kim
Osteoarthritis (OA) is characterized by a progressive loss of articular cartilage, subchondral bone sclerosis and synovial inflammation and is the most common chronic condition worldwide today. However, most treatments have focused on pain relief and OA symptoms. For these reasons, many ongoing studies are currently trying to develop efficient and successful therapies based on its pathology. Animal models that mimic the histopathology and symptoms of OA have a critical role in OA research and make it possible to investigate both secondary osteoarthritic changes due to a precedent event such as traumatic injury and naturally occurring changes for the development of therapeutics which can be tested in preclinical and clinical OA trials...
2018: PloS One
Anne Bernhardt, Birgit Paul, Michael Gelinsky
BACKGROUND: Collagens of marine origin are applied increasingly as alternatives to mammalian collagens in tissue engineering. The aim of the present study was to develop a biphasic scaffold from exclusively marine collagens supporting both osteogenic and chondrogenic differentiation and to find a suitable setup for in vitro chondrogenic and osteogenic differentiation of human mesenchymal stroma cells (hMSC). METHODS: Biphasic scaffolds from biomimetically mineralized salmon collagen and fibrillized jellyfish collagen were fabricated by joint freeze-drying and crosslinking...
March 13, 2018: Marine Drugs
Karen L Posey, Francoise Coustry, Jacqueline T Hecht
Cartilage oligomeric matrix protein (COMP) is a large pentameric glycoprotein that interacts with multiple extracellular matrix proteins in cartilage and other tissues. While, COMP is known to play a role in collagen secretion and fibrillogenesis, chondrocyte proliferation and mechanical strength of tendons, the complete range of COMP functions remains to be defined. COMPopathies describe pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), two skeletal dysplasias caused by autosomal dominant COMP mutations...
March 9, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
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
Frank J Simutis, Thomas P Sanderson, Gary D Pilcher, Michael J Graziano
The toxicity of avagacestat, a sulfonamide-based gamma (γ)-secretase inhibitor that was in development as a treatment for Alzheimer's disease, was evaluated in a comprehensive nonclinical toxicology program that included 6-month and 1-year repeat-dose toxicity studies in rats and dogs, respectively. There was a spectrum of mechanism-based changes attributed to inhibition of Notch signaling that regulates the differentiation and proliferation of cells throughout development and in adult tissues. In both rats and dogs, ovarian follicular degeneration and atrophy and a low incidence of granulosa cell hyperplasia and benign granulosa-thecal cell tumors were observed...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Qing Hu, Qing Chen, Xiuyun Yan, Bomei Ding, Dawei Chen, Lifang Cheng
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS: CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes...
March 12, 2018: Nanomedicine
Ryan R Kerney, James Hanken, David C Blackburn
Direct-developing amphibians form limbs during early embryonic stages, as opposed to the later, often postembryonic limb formation of metamorphosing species. Limb patterning is dramatically altered in direct-developing frogs, but little attention has been given to direct-developing salamanders. We use expression patterns of two genes, sox9 and col2a1, to assess skeletal patterning during embryonic limb development in the direct-developing salamander Plethodon cinereus. Limb patterning in P. cinereus partially resembles that described in other urodele species, with early formation of digit II and a generally anterior-to-posterior formation of preaxial digits...
March 12, 2018: Evolution & Development
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