The new frontier in systemic sclerosis: from epigenetics to new treatments

n/

Pathophysiology of Hemophilic Arthropathy

Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy—a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin—OPG; receptor activator of nuclear factor κB—RANK; RANK ligand—RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy

The crowded crossroad to angiogenesis in systemic sclerosis: where is the key to the problem?

In systemic sclerosis (SSc), peripheral vasculopathy is characterized by a progressive and irreversible loss of capillaries following endothelial cell injury, due to defects in both vascular repair and expected increase in new vessel growth (angiogenesis). The discovery of key molecular targets may help to develop the most effective therapeutic strategy for the SSc-related vasculopathy. A pathway worth targeting in SSc may include vascular endothelial growth factor, 165b isoform, an endogenous angiogenesis inhibitor abnormally expressed and released by different cell types, including activated endothelial cells and platelets

Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin-embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility

Morphological evidence of telocytes in human synovium

Abstract A new cell type named telocyte (i.e. cell with distinctive prolongations called telopodes) has recently been identified in the stroma of various organs in humans. However, no study has yet reported the existence of telocytes in the synovial membrane of diarthrodial joints. This work was therefore undertaken to search for telocytes in the normal human synovium using transmission electron microscopy, immunohistochemistry and immunofluorescence. Ultrastructural analyses demonstrated the presence of numerous spindle-shaped telocytes in the whole synovial sublining layer. Synovial telocytes exhibited very long and thin moniliform telopodes and were particularly concentrated at the boundary between the lining and sublining layers and around blood vessels. Light microscopy confirmed the presence of CD34-positive telocytes in the aforementioned locations. Moreover, synovial telocytes coexpressed CD34 and platelet-derived growth factor receptor α. Double immunostaining further allowed to unequivocally differentiate synovial telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). The in vitro examination of fibroblast-like synoviocyte primary cultures revealed the coexistence of different cell types, including CD34-positive telocytes projecting typical moniliform telopodes. In conclusion, our work provides the first evidence that telocytes do exist in the human synovium and lays the groundwork for future studies on synovial telocytes in a variety of degenerative and destructive joint diseases

Telocytes constitute a widespread interstitial meshwork in the lamina propria and underlying striated muscle of human tongue

Abstract Telocytes have recently emerged as unique interstitial cells defined by their extremely long, thin and moniliform prolongations termed telopodes. Despite growing evidence that these cells consistently reside in the stromal compartment of various organs from human beings, studies dealing with telocytes in structures of the oral cavity are scarce. Hence, the present morphologic study was undertaken to explore for the first time the presence and specific localization of telocytes within tissues of the normal human tongue, a complex muscular organ whose main functions include taste, speech, and food manipulation in the oral cavity. Telocytes were initially identified by CD34 immunostaining and confirmed by CD34/PDGFRα double immunofluorescence and transmission electron microscopy. CD34+/PDGFRα+ telocytes were organized in interstitial meshworks either in the tongue lamina propria or in the underlying striated muscle. Lingual telocytes were immunonegative for CD31, c-kit and α-SMA. Telopodes were finely distributed throughout the stromal space and concentrated beneath the lingual epithelium and around CD31+ vessels, skeletal muscle bundles/fibers, and intramuscular nerves and ganglia. They also enveloped salivary gland units outside the α-SMA+ myoepithelial cells and delimited lymphoid aggregates. These findings establish telocytes as a previously overlooked interstitial cell population worth investigating further in the setting of human tongue pathophysiology

Psychological well-being and quality of life in visually impaired baseball players: An Italian national survey

Italian baseball played by visually impaired and blind athletes is an adapted team sport which maintains the peculiar fast-moving features of this popular sport. It is also a mixed team game played together with sighted subjects. Here, we performed a national survey aimed at assessing the differences in psychological well-being (PWB) and quality of life (QoL) between visually impaired baseball players from Italian teams and non-players using a structured online questionnaire. Forty-three visually impaired baseball players and thirty-four visually impaired sedentary individuals completed a structured self-report survey including the validated 18-item Italian versions of the PWB (PWB-18) scale and the Short Form-12 (SF-12) questionnaire to assess the QoL. PWB-18 and SF-12 reference data from the Italian normally sighted population were also employed for comparison with the visually impaired baseball player group. Visually impaired baseball players reported better scores in all dimensions of the PWB-18 scale and significant higher scores in both physical and mental QoL evaluated by SF-12 than the non-player group. In addition, PWB-18 scale findings revealed significant differences between visually impaired baseball players and the reference normally sighted population consisting in lower scores for autonomy, environmental mastery, positive relations with others and purpose in life dimensions. Conversely, the mean scores for PWB-18 personal growth and self-acceptance dimensions were not significantly different between the two groups. The SF-12 questionnaire results demonstrated a significantly higher physical score in visually impaired players compared with the reference population. Instead, the SF-12 mental score of visually impaired athletes tended to be lower, though this difference was not statistically significant. Collectively, our findings suggest that the practice of Italian baseball may have a positive impact on PWB and QoL of visually impaired individuals

A loss of telocytes accompanies fibrotic remodelling of the colonic wall in ulcerative colitis

Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases in which the interaction of genetic, environmental and microbial factors drives chronic relapsing and remitting intestinal inflammation that finally leads to extensive tissue fibrosis. In UC, this results in a stiff, fibrotic colon unable to carry out peristalsis or to resorb fluids. Colonic dysmotility is often observed in UC patients and has been linked to severe damages of the enteric neural structures and a reduced density of interstitial cells of Cajal (ICC). Telocytes (TC), a peculiar type of stromal cells, have been recently identified in a variety of human tissues and organs, including the gastrointestinal tract. Several roles have been proposed for TC, including mechanical support, spatial relationships with different cell types, intercellular signalling and modulation of intestinal motility by spreading the slow waves generated by the pacemaker ICC. We have recently demonstrated that a loss of TC accompanies the fibrotic remodelling of the intestinal wall in CD patients. The aim of the present work was to investigate the presence and distribution of TC in colonic specimens from UC patients compared with controls. Archival paraffin-embedded full-thickness samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson’s trichrome to detect fibrosis. TC were identified by CD34 immunohistochemistry. Double immunofluorescence for CD34 and CD31 (vascular endothelial cells), alpha-SMA (smooth muscle cells, myofibroblasts) and c-kit (ICC) was also performed. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few TC were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. Conversely, numerous myofibroblasts were observed in the submucosa of all UC cases. In the muscle layers and at the myenteric plexus of early fibrotic UC, TC were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of TC was reduced or even completely absent around smooth muscle cells and myenteric plexus ganglia, paralleling the loss of the ICC network. In UC, the loss of TC accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility