Post-operative rehabilitation in osteoarthritis.

Osteoarthritis (OA) is a degenerative process involving the progressive loss of articular cartilage, synovial inflammation and structural changes to the subchondral bone that lead to loss of synovial joint structural features and impaired functionality of the articular cartilage. OA represents one of the most common causes of physical disability in the world. Different OA treatments are usually considered in relation to the stage of the disease. However, in the earlier stages of the disease, it is possible to recommend physical activity programs that can maintain joint health and keep the patient mobile, as recommended by the Osteoarthritis Research Society International (OARSI) and the European League Against Rheumatism (EULAR). In the most severe and advanced cases of OA, surgical intervention is necessary. In early post-operative stages, it is essential to include rehabilitation exercise program therapies in order to restore the full function of the involved joint. Physical therapy is crucial for the success of any surgical procedure and can promote recovery of muscle strength, range of motion, coordinated walking, proprioception and mitigate joint pain. After discharge from the hospital, patients should continue the rehabilitation exercise program at home. In this review, we analyze articles from the most recent literature and provide a balanced and comprehensive overview of the latest discoveries in relation to the effects of physical exercise on post-operative rehabilitation in OA. The literature search was conducted in April 2014 using PubMed, Scopus and Google Scholar using the keywords 'osteoarthritis', 'rehabilitation' and 'exercise', in a range of period 2002/2014 and out of 100 papers we have chosen 48 that we considered more appropriate. The available data suggests that physical exercise is effective, economical and accessible to everyone, and is one of the most important components of post-operative rehabilitation for OA

N-cadherin has a protective role in stable human atherosclerotic plaques: a morphological and immunohistochemical study

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CHI3L1 and lubricin expression in osteoarthritic cartilage

Osteoarthritis (OA) is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein 39 (GP-39) are known as a potential marker for the activation of chondrocytes and the progression of OA, whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren-Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology OARSI system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage. By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage. Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA evidenced in histomorphometric analysis of our samples, so that they could have a role in the daily clinical practice in staging the severity and progression of the disease.This work was supported by by a Grant-in-Aid provided by FIR 2014-2016, (cod. 314509), University of Catania, Italy

Identification of Novel Markers of Prostate Cancer Progression, Potentially Modulated by Vitamin D

Prostate cancer (PCa) is one of the most common cancers in men. The main risk factors associated with the disease include older age, family history of the disease, smoking, alcohol and race. Vitamin D is a pleiotropic hormone whose low levels are associated with several diseases and a risk of cancer. Here, we undertook microarray analysis in order to identify the genes involved in PCa. We analyzed three PCa microarray datasets, overlapped all genes significantly up-regulated, and subsequently intersected the common genes identified with the down-regulated genes transcriptome of LNCaP cells treated with 1α,25(OH)2D3, in order to identify the common genes involved in PCa and potentially modulated by Vitamin D. The analysis yielded 43 genes potentially involved in PCa and significantly modulated by Vitamin D. Noteworthy, our analysis showed that six genes (PRSS8, SOX4, SMYD2, MCCC2, CCNG2 and CD2AP) were significantly modulated. A Pearson correlation analysis showed that five genes out of six (SOX4 was independent), were statistically correlated with the gene expression levels of KLK3, and with the tumor percentage. From the outcome of our investigation, it is possible to conclude that the genes identified by our analysis are associated with the PCa and are potentially modulated by the Vitamin D

Beneficial effects of PACAP in osteoarthritis cartilage. An “in vivo” and an “in vitro” morphological and biochemical study

Osteoarthritis (OA); the most common form of degenerative joint disease; is associated with variations in pro-inflammatory growth factor levels; inflammation and hypocellularity resulting from chondrocyte apoptosis (1). Pituitary adenylate cyclaseactivating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several cell types; including chondrocytes (2). However; its role in OA has not been studied. To address this issue; we investigated whether PACAP expression is affected in OA cartilage obtained from experimentally-induced OA rat models; and then studied the effects of PACAP in isolated chondrocytes exposed to IL-1β in vitro to mimic the inflammatory milieu of OA cartilage. OA induction was established by histomorphometric and histochemical analyses. Changes in PACAP distribution in cartilage or its concentration in synovial fluid (SF) were assessed by immunohistochemistry and ELISA. Results showed that PACAP abundance in cartilage tissue and SF was high in healthy controls. OA induction decreased PACAP levels both in affected cartilage and SF. In vitro; PACAP prevented IL-1β-induced chondrocyte apoptosis; as determined by MTT assay; Hoechst staining and western blots of apoptotic-related proteins. These changes were also accompanied by decreased i-NOS and COX-2 levels; suggesting an anti-inflammatory effect. Altogether, these findings support a potential role for PACAP as a chondroprotective agent for the treatment of OA

Mesenchymal stem cell-based tissue engineering strategy for cartilage regeneration: A morphomolecular study

Articular cartilage is an avascular and aneural tissue with poor self-repair capacity. Pathological conditions leading to the cartilage degeneration, such as osteoarthritis (OA), have prompted the development of strategies aimed to its regeneration, such as mesenchymal stem cells (MSCs)-based tissue engineering approach. The aim of this study was to investigate if chondrocytes, differentiated from rat adipose tissue derived-MSCs (AMSCs) and seeded on Collagen Cell Carrier (CCC) scaffolds, are able to constitute a morphologically and biochemically healthy hyaline cartilage. To this purpose the AMSCs were primarily differentiated in chondrocytes through chondrogenic medium and subsequently cultured for 6 weeks on CCC scaffolds. The expression of osteoblast (Runt-related transcription factor 2 (RUNX2) and osteocalcin), chondrocyte (collagen I, II and lubricin) and apoptosis (caspase-3) biomarkers were evaluated in undifferentiated AMSCs, AMSCs-derived chondrocytes cultured in monolayer and AMSCs-derived chondrocytes seeded on CCC scaffolds, by different techniques such as immunohistochemistry, ELISA, Western blot and gene expression analyses. AMSCs-derived chondrocytes cultured on CCC scaffolds showed the increased expression of collagen II and lubricin, whereas the expression of collagen I, RUNX2, osteocalcin and caspase-3 resulted decreased when compared to the other groups. In conclusion, the results of this study suggest a possible role of AMSCs and the use of CCC scaffolds for therapeutic strategies aimed to the articular cartilage regeneration

Lubricin expression in an osteoarthritis rat model with Mediterranean Diet and mild physical activity to prevent cartilage degeneration

Osteoarthritis (OA) is a common musculoskeletal disorder characterized by slow progression and joint tissue degeneration [1]. Mediterranean Diet includes olive oil (OO), which have been shown to possess anti-inflammatory properties [2]. Regular and adequate physical activity reinforces joints, decreases bone loss and may be useful in the control of pain in patients with arthritis [1]. Lubricin is a chondroprotective glycoprotein and it serves as a critical boundary lubricant between opposing cartilage surfaces [1]. Its decreased expression predisposes to cartilage degeneration such as OA. The aim of this study was to evaluate the role of diet based on OO in conjugation with physical activity, on inflammation and on expression of lubricin in articular cartilage of rats, after injury. In this study we analyzed lubricin and interleukin-1 expression in cartilage and synovial fluid, by using histomorphometrical, morphological and biochemical analysis. The effects of anterior cruciate ligament transection decreased drastically the expression of lubricin and increased the expression of interleukin- 1 in rats, while after physical activity and OO, the values returned to a normal level compared to the control group. With our results we can confirm the importance of the physical activity in conjugation with OO diet in medical therapy to prevent OA disease in order to preserve the articular cartilage and then the entire joint

Chitotriosidase expression in monocyte-derived dendritic cells

Chitotriosidase (CHIT1) belongs to 18 glycosyl-hydrolase family, an ancient gene family that is widely expressed from prokaryotes to eukaryotes [1]. CHIT1 is a very critical enzyme to regulate the susceptibility to infection of organisms containing chitin as structural components. Conversely, during the development of acute/chronic inflammatory disorders, the enzymatic activity of CHIT1 increases significantly. The CHIT1 is expressed in activated macrophages as well in different lines monocyte-derived such as Kupffer cells and osteoclasts [2]. So far, it is unknown whether CHIT1 is expressed in other cells involved in the immune response such as monocyte-derived DCs. In this study we have investigated whether CHIT1 is produced in monocyte-derived DCs (moDCs) and the differential expression of CHIT1 during the different stage of moDCs differentiation. The presence of CHIT1 were examined by real time RT-PCR, Western Blot and Confocal Immunofluorescence, in Immature Dendritic cells (iDCs), generated from human monocytes by stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and in mature Dendritic cells (mDCs), obtained by using lipopolysaccharide (LPS) and interferon-gamma (IFN-g). We observed that CHIT1 was expressed during the DCs differentiation and maturation process in time dependent manner. The maturation of DCs showed a significantly increased expression of CHIT1 mRNA and protein. Furthermore, the CHIT1 was evenly distributed in cytoplasm both in iDCs and in mDCs. The enzymatic activity confirmed that CHIT1 could play a role in moDCs function. Taken together, our data confirm the crucial role of CHIT1 in primary immune responses and indicate that could be correlated with the immunogenicity of DCs

Expression and localization of CHI3L1 in monocyte derived dendritic cells

Chitinase-3-like-1 protein (CHI3L1) also called YKL-40, is a 40 kDa mammalian glycoprotein which is a heparin, chitin and collagen binding member of the mammalian chitinase-like proteins. Biological activities of CHI3L1 embrace regulation of cell proliferation, adhesion, angiogenesis, migration and activation. CHI3L1 is produced by variety of cells, including neutrophils, monocytes/macrophages, osteoclasts and Kupffer cells [1]. CHI3L1 secretion is induced by interferon (INF)-g and interleukin (IL)-6 and is an acute phase reactant associated with disease severity and mortality in a variety of infectious [2]. In this study, we have examined the expression and localization of CHI3L1 during the differentiation and maturation of monocyte derived dendritic cells by real time RT-PCR, Western Blot, Confocal Immunofluorescence, and Immunocytochemical assays. Potential nuclear localization signal (NLS) was determinated using the open source software cNLS Mapper and Chimera. Peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of DCs in time dependent manner. Furthermore, CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. In conclusion, the discovery of CHI3L1 expression in DCs has opened new dilemma for designing DC-based cancer immunotherapeutic. In fact, on the light of these results one can’t exclude that as well as activated Tumor-associated macrophages (TAMs) also DCs infiltration could to be a significant unfavorable prognostic factor for cancer patients

Guidelines for the use and interpretation of diagnostic methods in adult food allergy

Food allergy has an increasing prevalence in the general population and in Italy concerns 8 % of people with allergies. The spectrum of its clinical manifestations ranges from mild symptoms up to potentially fatal anaphylactic shock. A number of patients can be diagnosed easily by the use of first- and second-level procedures (history, skin tests and allergen specific IgE). Patients with complex presentation, such as multiple sensitizations and pollen-food syndromes, frequently require a third-level approach including molecular diagnostics, which enables the design of a component-resolved sensitization profile for each patient. The use of such techniques involves specialists' and experts' skills on the issue to appropriately meet the diagnostic and therapeutic needs of patients. Particularly, educational programs for allergists on the use and interpretation of molecular diagnostics are needed