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Cartilage biology

B L Farrugia, M S Lord, J M Whitelock, J Melrose
The development of bioscaffolds that incorporate chondroitin sulphate (CS) and their applications with progenitor and stem cells in cartilage, bone, cornea, skin, and neural repair are reviewed. CS is a heterogeneous structure due to the organisation of multiple CS disaccharide sulphation motifs, giving rise to a vast range of CS chain structures, and hence the wide range of biological activity. The incorporation of this biological molecule represents a significant advance in bioscaffold design and performance in tissue repair strategies...
March 21, 2018: Biomaterials Science
Eleni Zengini, Konstantinos Hatzikotoulas, Ioanna Tachmazidou, Julia Steinberg, Fernando P Hartwig, Lorraine Southam, Sophie Hackinger, Cindy G Boer, Unnur Styrkarsdottir, Arthur Gilly, Daniel Suveges, Britt Killian, Thorvaldur Ingvarsson, Helgi Jonsson, George C Babis, Andrew McCaskie, Andre G Uitterlinden, Joyce B J van Meurs, Unnur Thorsteinsdottir, Kari Stefansson, George Davey Smith, Jeremy M Wilkinson, Eleftheria Zeggini
Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis...
March 20, 2018: Nature Genetics
Jehan J El-Jawhari, Claire L Brockett, Ioannis Ktistakis, Elena Jones, Peter V Giannoudis
The ankle degeneration ranging from focal osteochondral lesions to osteoarthritis can cause a total joint function loss. With rising life expectancy and activity of the patients, various regenerative therapies were introduced aiming to preserve the joint function via the induction of cartilage and bone repair. Here, biological events and mechanical changes of the ankle degeneration were discussed. The regenerative therapies were reviewed versus the standard surgical treatment. We especially focused on the use of mesenchymal (multipotential) stromal cells (MSCs) highlighting their dual functions of regeneration and cell modulation with an emphasis on the emerging MSC-based clinical studies...
March 19, 2018: Regenerative Medicine
Sònia Font Tellado, Silvia Chiera, Walter Bonani, Patrina S P Poh, Claudio Migliaresi, Antonella Motta, Elizabeth R Balmayor, Martijn van Griensven
The tendon/ligament-to-bone transition (enthesis) is a highly specialized interface tissue with structural gradients of extracellular matrix composition, collagen molecule alignment and mineralization. These structural features are essential for enthesis function, but are often not regenerated after injury. Tissue engineering is a promising strategy for enthesis repair. Engineering of complex tissue interfaces such as the enthesis is likely to require a combination of biophysical, biological and chemical cues to achieve functional tissue regeneration...
March 14, 2018: Acta Biomaterialia
Arantza Infante, Clara I Rodríguez
Aging is a complex biological process, which involves multiple mechanisms with different levels of regulation. Senescent cells are known to secrete senescence-associated proteins, which exert negative influences on surrounding cells. Mesenchymal stem cells (MSCs), the common progenitors for bone, cartilage and adipose tissue (which are especially affected tissues in aging), are known to secrete a broad spectrum of biologically active proteins with both paracrine and autocrine functions in many biological processes...
March 15, 2018: Scientific Reports
Ruijun He, Baichuan Wang, Min Cui, Zekang Xiong, Hui Lin, Lei Zhao, Zhiliang Li, Zhe Wang, Shaun Peggrem, Zhidao Xia, Zengwu Shao
Background: Link protein N-terminal peptide (LPP) in extracellular matrix (ECM) of cartilage could induce synthesis of proteoglycans and collagen type II in cartilaginous cells. Cartilage stem/progenitor cells (CSPCs), the endogenous stem cells in cartilage, are important in cartilage degeneration and regeneration. We hypothesized that LPP could be a stimulator for stem cell-based cartilage regeneration by affecting biological behaviors of CSPC. Methods: CSPCs were isolated from rat knee cartilage...
2018: Stem Cells International
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
Yoshiya Tanaka
Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammation and joint damage that causes significant morbidity and mortality. Rapid and appropriate intervention using disease-modifying anti-rheumatic drugs(DMARDs)is prerequisite to halt joint destruction and long-term functional disabilities. Recent progress in the treatment strategy has brought about paradigm shift for the management of the disease, namely, the combined use of methotrexate, a synthetic DMARD, and a biologic DMARD targeting TNF, IL-6 and T cells has revolutionized treatment of rheumatoid arthritis...
2018: Clinical Calcium
Riko Nishimura, Kenji Hata, Eriko Nakamura
Chondrocytes, which are originated from undifferentiated mesenchymal stem cells, play roles in skeletal development and growth in mammal, and smooth movement of joints. Endochondral ossification is necessary for skeletal development, and the multiple and complex biological events are precisely regulated by several hormones, cytokines, and their downstream signaling and transcriptional regulation. On the other hands, articular chondrocytes physiologically retains their features during a lifetime. Numerous molecules involved in endochondral ossification have been identified and investigation of the molecular mechanisms have amazingly progressed...
2018: Clinical Calcium
Kazuto Hoshi, Yuko Fujihara, Takanori Yamawaki, Motohiro Harai, Yukiyo Asawa, Atsuhiko Hikita
Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential...
March 6, 2018: Histochemistry and Cell Biology
Tomoya Sakabe, Keiko Sakai, Toru Maeda, Ataru Sunaga, Nao Furuta, Ronen Schweitzer, Takako Sasaki, Takao Sakai
Tendon is a dense connective tissue that transmits high mechanical forces from skeletal muscle to bone. The transcription factor scleraxis (Scx) is a highly specific marker of both precursor and mature tendon cells (tenocytes). Mice lacking scx exhibit a specific and virtually complete loss of tendons during development. However, the functional contribution of Scx to wound healing in adult tendon has not yet been fully characterized. Here, using ScxGFP-tracking and loss-of-function systems, we show in an adult mouse model of Achilles tendon injury that paratenon cells, representing a stem cell antigen-1 (Sca-1)-positive and Scx-negative progenitor subpopulation, display Scx induction, migrate to the wound site, and produce extracellular matrix (ECM) to bridge the defect, whereas resident tenocytes exhibit a delayed response...
March 5, 2018: Journal of Biological Chemistry
N M Astakhova, A V Korel', E I Shchelkunova, K E Orishchenko, S V Nikolaev, U S Zubairova, I A Kirilova
We isolated and characterized cultures of bone and cartilage tissue cells of laboratory minipigs. The size and morphological features of adherent osteogenic and chondrogenic cells were specified. During long-term culturing under standard conditions, the studied cultures expressed specific markers that were detected by immunohistochemical staining: alkaline phosphatase and calcium deposits in osteoblasts and type II collagen and cartilage extracellular matrix in chondrogenic cells. Proliferative potential (mitotic index) of both cell types was 4...
March 5, 2018: Bulletin of Experimental Biology and Medicine
Jaicy Jacob, Namdev More, Kiran Kalia, Govinda Kapusetti
Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions...
2018: Inflammation and Regeneration
Denada Dibra, Xueqing Xia, Mihai Gagea, Guillermina Lozano, Shulin Li
Spondyloarthropathies, the second most frequently occurring form of chronic inflammatory arthritis, affects young adults in particular. However, a proper model with which to study the biology of this disease and to develop therapeutics is lacking. One of the most accepted animal models for this disease uses HLA-B27/Hu-β2m transgenic rats; however, only 30%-50% of male HLA-B27/Hu-β2m rats develop spontaneous, clinically apparent spondylitis and have a variable time until disease onset. Here, we report a high-incidence, low-variation spontaneous mouse model that delineates how the combination of inflammatory cytokine interleukin-27 (IL-27) signaling deficiency and mitogenic signaling (mutant p53R172H) in vivo, leads to bone loss in the vertebral bodies and ossification of the cartilage in the intervertebral discs...
2018: PloS One
A A Shetty, S J Kim, S Ahmed, S Trattnig, S A Kim, H J Jang
Introduction The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation...
March 2018: Annals of the Royal College of Surgeons of England
Huijuan Shi, Wenfang Chen, Yu Dong, Xiaofang Lu, Wenhui Zhang, Liantang Wang
To investigate the roles of B‑cell lymphoma‑2 associated athanogene 3 (BAG3) in human chondrosarcoma and the potential mechanisms, the expression levels of BAG3 were detected in the present study, and the associations between BAG3 and clinical pathological parameters, clinical stage as well as the survival of patients were analyzed. The present study detected BAG3 mRNA and protein expression in the normal cartilage cell line HC‑a and in SW1353 chondrosarcoma cells by reverse transcription‑quantitative polymerase chain reaction and western blot analysis...
February 15, 2018: Molecular Medicine Reports
Shangkun Tang, Qian Tang, Jialei Jin, Gang Zheng, Jianchen Xu, Wu Huang, Xiaobin Li, Ping Shang, Haixiao Liu
Osteoarthritis (OA), which is characterized by progressive degradation of the articular cartilage, is the most prevalent form of human arthritis. Accumulating evidence has shown that polydatin (PD) exerts special biological functions in a variety of diseases. However, whether it protects against OA development has remained unknown. Here, we investigated the anti-inflammatory and chondroprotective effects of PD on interleukin (IL)-1β-induced human osteoarthritic chondrocytes and in the surgical destabilization of medial meniscus mouse (DMM) OA models...
February 27, 2018: Food & Function
Yan Jing, Junjun Jing, Ke Wang, Kevin Chan, Stephen E Harris, Robert J Hinton, Jian Q Feng
A recent breakthrough showing that direct trans-differentiation of chondrocytes into bone cells commonly occurs during endochondral bone formation in the growth plate, articular cartilage, and mandibular condylar cartilage suggests that chondrogenesis and osteogenesis are likely one continuous biological process instead of two separate processes. Yet, gene regulation of this cell transformation is largely unclear. Here, we employed cartilage-specific β-catenin loss-of-function ( β-cateninfx/fx ) and gain-of-function ( β-cateninfx(exon3)/ fx(exon3) ) models in the R26R Tomato background (for better tracing the cell fate of chondrocytes) to study the role of β-catenin in cell trans-differentiation...
2018: International Journal of Biological Sciences
Chen Chu, Wu Chunshuai, Chen Jiajia, Zhang Jinlong, Xue Pengfei, Jiang Jiawei, Cui Zhiming
Circular RNAs are newly identified RNAs that regulate gene expression and execute various biological activities. Facet joint osteoarthritis (FJOA) is a severe facet joint cartilage degeneration disease that induces chronic low back pain to a larger population. The molecular mechanisms of FJOA, especially the presence and changes of circular RNAs in FJOA have not been investigated. In the current study, we analyzed RNA deep sequencing outcomes from healthy control group and FJOA group, identified and annotated circular RNAs, and determined the expressions of circular RNAs...
February 19, 2018: Biochemical and Biophysical Research Communications
Magdalena Krajewska-Włodarczyk, Agnieszka Owczarczyk-Saczonek, Waldemar Placek, Adam Osowski, Joanna Wojtkiewicz
Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products...
February 22, 2018: International Journal of Molecular Sciences
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