The synovial surface of the articular cartilage

The articular cartilage has been the subject of a huge amount of research carried out with a wide array of different techniques. Most of the existing morphological and ultrastructural data on the this tissue, however, were obtained either by light microscopy or by transmission electron microscopy. Both techniques rely on thin sections and neither allows a direct, face-on visualization of the free cartilage surface (synovial surface), which is the only portion subject to frictional as well as compressive forces. In the present research, high resolution visualization by scanning electron microscopy and by atomic force microscopy revealed that the collagen fibrils of the articular surface are exclusively represented by thin, uniform, parallel fibrils evocative of the heterotypic type IX-type II fibrils reported by other authors, immersed in an abundant matrix of glycoconjugates, in part regularly arranged in phase with the D-period of collagen. Electrophoresis of fluorophore-labeled saccharides confirmed that the superficial and the deeper layers are quite different in their glycoconjugate content as well, the deeper ones containing more sulfated, more acidic small proteoglycans bound to thicker, more heterogenous collagen fibrils. The differences found between the synovial surface and the deeper layers are consistent with the different mechanical stresses they must withstand

Revisiting the hallmarks of cancer: The role of hyaluronan

Extracellular matrix (ECM) is a complex network of macromolecules such as proteoglycans (PGs), glycosaminoglycans (GAGs) and fibrous proteins present within all tissues and organs. The main role of ECM is not only to provide an essential mechanical scaffold for the cells but also to mediate crucial biochemical cues that are required for tissue homeostasis. Dysregulations in ECM deposition alter cell microenvironment, triggering the onset or the rapid progression of several diseases, including cancer. Hyaluronan (HA) is a ubiquitous component of ECM considered as one of the main players of cancer initiation and progression. This review discusses how HA participate in and regulate several aspects of tumorigenesis, with particular attention to the hallmarks of cancer proposed by Hanahan and Weinberg such as sustaining of the proliferative signaling, evasion of apoptosis, angiogenesis, activation of invasion and metastases, reprogramming of energy metabolism and evasion of immune response

Ha and hs changes in endothelial inflammatory activation

Cardiovascular diseases are a group of disorders caused by the presence of a combination of risk factors, such as tobacco use, unhealthy diet and obesity, physical inactivity, etc., which cause the modification of the composition of the vessel’s matrix and lead to the alteration of blood flow, matched with an inflammation condition. Nevertheless, it is not clear if the inflammation is a permissive condition or a consequent one. In order to investigate the effect of inflammation on the onset of vascular disease, we treated endothelial cells with the cytokine TNF-α that is increased in obese patients and is reported to induce cardiometabolic diseases. The inflammation induced a large change in the extracellular matrix, increasing the pericellular hyaluronan and altering the heparan sulfate Syndecans sets, which seems to be related to layer permeability but does not influence cell proliferation or migration nor induce blood cell recruitment or activation

The secreted protein c10orf118 is a new regulator of hyaluronan synthesis involved in tumour-stroma cross-talk

Interaction between cancer cells and their microenvironment is central in defining the fate of cancer development. Tumour cells secrete signals (cytokines, chemokines, growth factors) that modify the surrounding area, while the niche supplies structures and activities necessary for tumour maintenance and growth. Hyaluronan (HA) is a glycosaminoglycan that constitute cancer cell niche and is known to influence tumour functions such as proliferation, migration and neoangiogenesis. The knowledge of the factors regulating HA synthesis and size is crucial in understanding the mechanisms sustaining tumour development. Here we show that a yet uncharacterized protein secreted by breast tumour cell lines, named c10orf118 (accession number NM_018017 in NCBI/BLAST, and Q7z3E2 according to the Uniprot identifier), with a predicted length of 898 amino acids, can induce the secretion of HA by stromal fibroblasts through the up-regulation of the hyaluronan synthase 2 gene (HAS2). Intracellularly, this protein is localized in the Golgi apparatus with a possible role in vesicle maturation and transport. The expression of c10orf118 was verified in breast cancer patient specimens and was found to be associated with the presence of estrogen receptor that characterizes a good patient survival. We suggest c10orf118 as a new player that influences the HA amount in breast cancer microenvironment and is associated with low aggressiveness of cancer