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Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis.

26 min 54 sec ago
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Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis.

Sci Rep. 2017 May 17;7(1):2029

Authors: Kolhe R, Hunter M, Liu S, Jadeja RN, Pundkar C, Mondal AK, Mendhe B, Drewry M, Rojiani MV, Liu Y, Isales CM, Guldberg RE, Hamrick MW, Fulzele S

Abstract
The pathogenesis of osteoarthritis (OA) is poorly understood, and therapeutic approaches are limited to preventing progression of the disease. Recent studies have shown that exosomes play a vital role in cell-to-cell communication, and pathogenesis of many age-related diseases. Molecular profiling of synovial fluid derived exosomal miRNAs may increase our understanding of OA progression and may lead to the discovery of novel biomarkers and therapeutic targets. In this article we report the first characterization of exosomes miRNAs from human synovial fluid. The synovial fluid exosomes share similar characteristics (size, surface marker, miRNA content) with previously described exosomes in other body fluids. MiRNA microarray analysis showed OA specific exosomal miRNA of male and female OA. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified gender-specific target genes/signaling pathways. These pathway analyses showed that female OA specific miRNAs are estrogen responsive and target TLR (toll-like receptor) signaling pathways. Furthermore, articular chondrocytes treated with OA derived extracellular vesicles had decreased expression of anabolic genes and elevated expression of catabolic and inflammatory genes. In conclusion, synovial fluid exosomal miRNA content is altered in patients with OA and these changes are gender specific.

PMID: 28515465 [PubMed - in process]

Competitive Protein Binding Influences Heparin-Based Modulation of Spatial Growth Factor Delivery for Bone Regeneration.

Fri, 2017-05-19 05:30

Competitive Protein Binding Influences Heparin-Based Modulation of Spatial Growth Factor Delivery for Bone Regeneration.

Tissue Eng Part A. 2017 Mar 24;:

Authors: Hettiaratchi MH, Chou C, Servies N, Smeekens JM, Cheng A, Esancy C, Wu R, McDevitt TC, Guldberg RE, Krishnan L

Abstract
Tissue engineering strategies involving the in vivo delivery of recombinant growth factors are often limited by the inability of biomaterials to spatially control diffusion of the delivered protein within the site of interest. The poor spatiotemporal control provided by porous collagen sponges, which are used for the clinical delivery of bone morphogenetic protein-2 (BMP-2) for bone regeneration, has necessitated the use of supraphysiological protein doses, leading to inflammation and heterotopic ossification. This study describes a novel tissue engineering strategy to spatially control rapid BMP-2 diffusion from collagen sponges in vivo by creating a high-affinity BMP-2 sink around the collagen sponge. We designed an electrospun poly-ɛ-caprolactone nanofiber mesh containing physically entrapped heparin microparticles, which have been previously demonstrated to bind and retain large amounts of BMP-2. Nanofiber meshes containing 0.05 and 0.10 mg of microparticles/cm(2) demonstrated increased BMP-2 binding and decreased BMP-2 release in vitro compared with meshes without microparticles. However, when microparticle-containing meshes were used in vivo to limit the diffusion of BMP-2 delivered by using collagen sponges in a rat femoral defect, no differences in heterotopic ossification or biomechanical properties were observed. Further investigation revealed that, although BMP-2 binding to heparin microparticles was rapid, the presence of serum components attenuated microparticle-BMP-2 binding and increased BMP-2 release in vitro. These observations provide a plausible explanation for the results observed in vivo and suggest that competitive protein binding in vivo may hinder the ability of affinity-based biomaterials to modulate growth factor delivery.

PMID: 28338419 [PubMed - as supplied by publisher]

Supraspinatus tendon overuse results in degenerative changes to tendon insertion region and adjacent humeral cartilage in a rat model.

Sun, 2017-03-26 03:30
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Supraspinatus tendon overuse results in degenerative changes to tendon insertion region and adjacent humeral cartilage in a rat model.

J Orthop Res. 2016 Dec 21;:

Authors: Parks AN, McFaline-Figueroa J, Coogan A, Poe-Yamagata E, Guldberg RE, Platt MO, Temenoff JS

Abstract
The etiology of rotator cuff tendon overuse injuries is still not well understood. Furthermore, how this overuse injury impacts other components of the glenohumeral joint, including nearby articular cartilage, is also unclear. Therefore, this study sought to better understand the time course of tendon protease activity in a rat model of supraspinatus overuse, as well as determine effects of 10 weeks of overuse on humeral head articular cartilage. For these studies, multiplex gelatin zymography was used to characterize protease activity profiles in tendon and cartilage, while histological scoring/mechanical testing and micro-computed tomography (μCT) imaging were used to quantify structural damage in the supraspinatus tendon insertion and humeral articular cartilage, respectively. Histological scoring of supraspinatus tendon insertions revealed tendinopathic cellular and collagen fiber changes after 10 weeks of overuse when compared to controls, while mechanical testing revealed no significant differences between tensile moduli (overuse: 24.5 ± 11.5 MPa; control: 16.3 ± 8.7 MPa). EPIC-μCT imaging on humeral articular cartilage demonstrated significant cartilage thinning (overuse: 119.6 ± 6.34 μm; control: 195.4 ± 13.4μm), decreased proteoglycan content (overuse: 2.1 ± 0.18 cm(-1) ; control: 1.65 ± 0.14 cm(-1) ), and increased subchondral bone thickness (overuse: 216.2 ± 10.9 μm; control: 192 ± 17.8μm) in the overuse animals. Zymography results showed no significant upregulation of cathepsins or matrix metalloproteinases in tendon or cartilage at 2 or 10 weeks of overuse compared to controls. These results have further elucidated timing of protease activity over 10 weeks and suggest that damage occurs to other tissues in addition to the supraspinatus tendon in this overuse injury model. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID: 28001327 [PubMed - as supplied by publisher]

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