Synovial membrane asks for independence

Synovial membrane is traditionally considered as a part of the joint capsule. It, however, differs from fibrous part of the capsule in development, structure, function, vascularisation, innervation and involvement in pathological processes. Moreover, in some areas, it even does not contact with the fibrous capsule. Thus, it appears that the synovial membrane should be considered as an independent organ and not as the lining of the joint capsule.

Formation of synovial joints and articular cartilage

Chondrocytes differentiate from mesenchymal progenitors and produce templates(anlagen) for the developing bones. Chondrocyte differentiation is controlled bySox transcription factors. Templates for the neighbour bones are subsequentlyseparated by conversion of differentiated chondrocytes into non-chondrogeniccells and emergence of interzone in which joints cavitation occurs. A central rolein initiating synovial joint formation plays Wnt-14/beta-catenin signalling pathway.Moreover, bone morphogenetic proteins and growth and differentiation factorsare expressed at the site of joint formation. Joint cavitation is associated withincreased hyaluronic acid synthesis. Hyaluronic acid facilitates tissue separationand creation of a functional joint cavity. According to the traditional view articularcartilage represents part of cartilage anlage that is not replaced by bone throughendochondral ossification. Recent studies indicate, however, that peri-joint mesenchymalcells take part in interzone formation and that these interzone cellssubsequently differentiate into articular chondrocytes and synovial cells. Thus,anlage chondrocytes have a transient character and disappear after cessation ofgrowth plate function while articular chondrocytes have stable and permanentphenotype and function throughout life

Triggering of the dsRNA Sensors TLR3, MDA5, and RIG-I Induces CD55 Expression in Synovial Fibroblasts

Background: CD55 (decay-accelerating factor) is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS). CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS. Methods: FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR) ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C)) and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (ds)RNA sensors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I). CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry. Results: CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA), osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1 beta and especially by the TLR3 ligand poly(I:C). Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55. Conclusions: Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocyte

Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

Background: Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance. Methods: We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance. Results: HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin. Conclusions: Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC transporter expression. The HA-CD44 signaling pathway is therefore a promising target in platinum resistant ovarian cancer.Carmela Ricciardelli, Miranda P Ween, Noor A Lokman, Izza A Tan, Carmen E Pyragius, and Martin K Oehle

Vertebral endplate abnormalities are highly associated with thoracic disc herniations in symptomatic patients

Poster presentation: GP128Background: Lumbar disc herniations are common. Endplate abnormalities (e.g. Schmorl's node) have been noted to occur throughout the lumbar spine, with or without disc herniation. However, disc herniations of the thoracic spine and are often associated with neurological sequelae, frequently necessitating surgery which has a high incidence of complications. Unlike the lumbar spine, the mechanism of thoracic disc herniations is not well understood. Recently, a much thorough understanding of the endplate phenotype has been proposed that provides insight into the etiology and risk of disc changes. The following largescale study was performed in a cohort of symptomatic thoracic disc herniation patients to determine the relationship between such lesions and the role of endplate abnormalities as well as other MRI phenotypes. Methods: A retrospective review of a prospectively collected cohort of 161 adult patients who were diagnosed with symptomatic thoracic disc herniation and myelopathy requiring surgery from 2008 to 2012 at a single institute were assessed. Preoperative T2-weighted MRIs were assessed of the thoracic spine. Imaging phenotypes of black disc, disc space narrowing, disc herniations, Modic changes, endplate abnormalities, osteophytes and ossified longitudinal ligament were assessed from T1-L1. Results: There were 49% males and 51% females. Black disc was noted in 75% of patients, most prevalent at T8/9 (32%), T7/8 (29%) and T6/7 (27.3%). Disc space narrowing was noted in 31% of the patients, mainly occurring at T11/12 (6.8%), T8/9 (8.1%) and T6/7 (7%). Disc herniation was more prevalent at T11/12 (60%), T12/L1 (55%), T10/11 (50%), T8/9 (42.9%) and T9/10 (37%). Endplate abnormalities were noted in 84% of the patients, occurring primarily at T11/12 (48%), T9/10 (33%), T12/L1 (32%) and T10/11 (44%), and strongly associated with levels of disc herniation. Modic changes were noted in 32% of patients, primarily occurring at T6/7 (11%), T7/8 (11%), and T8/9 (10%). Osteophytes occurred in 4% of the patients and were more common at the lower thoracic spine at T10-L1. Ossified longitudinal ligament was noted in 20% of the patients, mainly noted at T6-T9. Discussion: This study represents one of the largest cohort of patients with symptomatic thoracic disc herniation and the imaging assessment of additional spinal phenotype patterns. Findings from this study have noted that endplate abnormalities are highly associated in patients with symptomatic thoracic pathology, mainly occurring at levels of disc herniations. Secondary degenerative phenotypes were also noted, mainly occurring in the lower thoracic spine but presenting with unique topographical and morphological patterns. Having a better understanding of the endplate phenotype and the occurrence of thoracic disc herniation may shed light into the etiology and mechanism of endplate and disc pathology, which may also shed light upon the prediction of future spinal conditions of the thoracic spine

Possible Association Between Zika Virus Infection And Microcephaly - Brazil, 2015

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