Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly (ethylene glycol) diacrylate scaffold

Osteoarthritis (OA) is characterized by degenerative changes within joints that involved quantitative and/or qualitative alterations of cartilage and synovial fluid lubricin, a mucinous glycoprotein secreted by synovial fibroblasts and chondrocytes. Modern therapeutic methods, including tissue-engineering techniques, have been used to treat mechanical damage of the articular cartilage but to date there is no specific and effective treatment. This study aimed at investigating lubricin immunohistochemical expression in cartilage explant from normal and OA patients and in cartilage constructions formed by Poly (ethylene glycol) (PEG) based hydrogels (PEG-DA) encapsulated OA chondrocytes. The expression levels of lubricin were studied by immunohistochemistry: i) in tissue explanted from OA and normal human cartilage; ii) in chondrocytes encapsulated in hydrogel PEGDA from OA and normal human cartilage. Moreover, immunocytochemical and western blot analysis were performed in monolayer cells from OA and normal cartilage. The results showed an increased expression of lubricin in explanted tissue and in monolayer cells from normal cartilage, and a decreased expression of lubricin in OA cartilage. The chondrocytes from OA cartilage after 5 weeks of culture in hydrogels (PEGDA) showed an increased expression of lubricin compared with the control cartilage. The present study demonstrated that OA chondrocytes encapsulated in PEGDA, grown in the scaffold and were able to restore lubricin biosynthesis. Thus our results suggest the possibility of applying autologous cell transplantation in conjunction with scaffold materials for repairing cartilage lesions in patients with OA to reduce at least the progression of the disease

Effects of exposure to fluoro-edenite fibre pollution on the respiratory system: an in vivo model

An increased standardised rate of mortality from pleural mesothelioma among the population of Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite fibres. Our aim was to establish whether and how these fibres may induce pathological effects using an in vivo model. Lung tissue collected from 60 healthy sheep selected from six flocks habitually grazing near Biancavilla and from 10 control sheep was fixed formalin and paraffinembedded; sections were stained with haematoxylineosin, Masson trichrome and Gomori argentic impregnation. Histochemical studies and immunohistochemical analysis for the localisation of TRAIL, DR5 and MMP13 were also performed. The lungs of exposed sheep exhibited fibrosis and loss of alveolar architecture with honeycombing of alveolar cavities. Fluoro-edenite fibres were detected close to the alveolar epithelium and interstitia. The parenchyma showed hyaline degeneration and strong PAS-positivity in the interstitium, proteoglycan alterations, reflecting a damaged basal membrane and an involvement of the interstitial matrix. MMP-13 was overexpressed, mainly in fibroblasts and epithelial cells, while positivity for TRAIL and DR5 was detected on alveolar surfaces and in the vascular stroma. The initial pathological event seems to involve first the alveoli and subsequently the interstitium, giving rise to classic honeycombing. The triggering event at the level of type I pneumocytes would damage the cytoplasmic membrane resulting in loss of cell elements and exposure of underlying capillaries, and eventually in a series of reactions including macrophage activation, possible release of growth factors and metaplasic reconstruction of lung alveoli. Immunopositivity for TRAIL and MMP-13 receptor suggests that apoptotic processes may also be activated by fluoro-edenite

Fluoro-edenite fibres induce lung cell apoptosis, an in vivo study

We previously showed that apoptosis in the lungs of sheep exposed to fluoro-edenite fibres is induced via the receptor pathway. The present study was performed to gain further insights into the mechanisms of activation of programmed cell death induced by the fibres. Fluoro-edenite fibres are similar in size and morphology to some amphibolic asbestos fibres. They have been found in benmoreitic lavas, in the local stone quarry, in building materials and in road paving at Biancavilla, a town in eastern Sicily (Italy), where epidemiological surveys revealed a cluster of mortality from pleural mesothelioma. Inhalation of asbestos fibres can cause chronic inflammation and carcinogenesis. Since fluoro-edenite has been shown to activate the apoptotic process, we set out to characterise the expression of apoptosis-regulating proteins in fluoroedenite- exposed lung disease and sought to determine if apoptosis results from fluoro-edenite exposure. Lung tissue from apparently healthy sheep habitually grazing near Biancavilla was processed for immunohistochemical localisation of bcl-2 and bax. Results showed epithelial and interstitial bax overexpression, especially in cells directly in contact with the fibres, and negative bcl-2 immunoexpression. TUNEL-positive cells were detected in alveoli and connective tissue. The integrity of alveolar epithelium and alveolar apoptosis are critical determinants in the pathways that initiate fibrogenesis in the lung and fibroblastic foci are usually found close to abnormal or denuded alveolar epithelium. Our results are consistent with the hypothesis that apoptosis is an important mechanism for removing cells with irreparable fluoro-edenite-induced genetic changes that predispose them to a neoplastic evolution

Anatomia Umana

Testo di anatomia Umana per Lauree Sanitarie e Scienze Motori