Facing Back Pain with Wine and Physical Activity.

Intervertebral disc disease (IVDD) refers to degenerative processes of the spine resulting in reduced shock-absorbing ability, which may ultimately lead to disc herniation and spinal cord compression. Back pain is associated with this condition, representing the clinical feature mostly frequently referred by the patients. In this contribution, we analysed a recent review published in the Journal of Investigative Surgery, which discusses the mechanisms of the ROS production in IVDD with respect to resveratrol activity.

Current knowledge of pituitary adenylate cyclase activating polypeptide (PACAP) in articular cartilage.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionally well conserved neuropeptide, mainly expressed by neuronal and peripheral cells. It proves to be an interesting object of study both for its trophic functions during the development of several tissues and for its protective effects against oxidative stress, hypoxia, inflammation and apoptosis in different degenerative diseases. This brief review summarises the recent findings concerning the role of PACAP in the articular cartilage. PACAP and its receptors are expressed during chondrogenesis and are shown to activate the pathways involved in regulating cartilage development. Moreover, this neuropeptide proves to be chondroprotective against those stressors that determine cartilage degeneration and contribute to the onset of osteoarthritis (OA), the most common form of degenerative joint disease. Indeed, the degenerated cartilage exhibits low levels of PACAP, suggesting that its endogenous levels in adult cartilage may play an essential role in maintaining physiological properties. Thanks to its peculiar characteristics, exogenous administration of PACAP could be suggested as a potential tool to slow down the progression of OA and for cartilage regeneration approaches.

Evaluation of a Cell-Free Collagen Type I-Based Scaffold for Articular Cartilage Regeneration in an Orthotopic Rat Model.

The management of chondral defects represents a big challenge because of the limited self-healing capacity of cartilage. Many approaches in this field obtained partial satisfactory results. Cartilage tissue engineering, combining innovative scaffolds and stem cells from different sources, emerges as a promising strategy for cartilage regeneration. The aim of this study was to evaluate the capability of a cell-free collagen I-based scaffold to promote cartilaginous repair after orthotopic implantation in vivo. Articular cartilage lesions (ACL) were created at the femoropatellar groove in rat knees and cell free collagen I-based scaffolds (S) were then implanted into right knee defect for the ACL-S group. No scaffold was implanted for the ACL group. At 4-, 8- and 16-weeks post-transplantation, degrees of cartilage repair were evaluated by morphological, histochemical and gene expression analyses. Histological analysis shows the formation of fibrous tissue, at 4-weeks replaced by a tissue resembling the calcified one at 16-weeks in the ACL group. In the ACL-S group, progressive replacement of the scaffold with the newly formed cartilage-like tissue is shown, as confirmed by Alcian Blue staining. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses display the expression of typical cartilage markers, such as collagen type I and II (ColI and ColII), Aggrecan and Sox9. The results of this study display that the collagen I-based scaffold is highly biocompatible and able to recruit host cells from the surrounding joint tissues to promote cartilaginous repair of articular defects, suggesting its use as a potential approach for cartilage tissue regeneration.

Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study.

Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG's ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG-CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG's cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG-CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches.

Functional Biomolecule Delivery Systems and Bioengineering in Cartilage Regeneration.

Osteoarthritis (OA) is a common degenerative disease which involves articular cartilage, and leads to total joint disability in the advanced stages. Due to its avascular and aneural nature, damaged cartilage cannot regenerate itself. Stem cell therapy and tissue engineering represent a promising route in OA therapy, in which cooperation of mesenchymal stem cells (MSCs) and three-dimensional (3D) scaffolds contribute to cartilage regeneration. However, this approach still presents some limits such as poor mechanical properties of the engineered cartilage. The natural dynamic environment of the tissue repair process involves a collaboration of several signals expressed in the biological system in response to injury. For this reason, tissue engineering involving exogenous "influencers" such as mechanostimulation and functional biomolecule delivery systems (BDS), represent a promising innovative approach to improve the regeneration process. BDS provide a controlled release of biomolecules able to interact between them and with the injured tissue. Nano-dimensional BDS is the future hope for the design of personalized scaffolds, able to overcome the delivery problems. MSC-derived extracellular vesicles (EVs) represent an attractive alternative to BDS, due to their innate targeting abilities, immunomodulatory potential and biocompatibility. Future advances in cartilage regeneration should focus on multidisciplinary strategies such as modular assembly strategies, EVs, nanotechnology, 3D biomaterials, BDS, mechanobiology aimed at constructing the functional scaffolds for actively targeted biomolecule delivery. The aim of this review is to run through the different approaches adopted for cartilage regeneration, with a special focus on biomaterials, BDS and EVs explored in terms of their delivery potential, healing capabilities and mechanical features.

Moderate Physical Activity as a Prevention Method for Knee Osteoarthritis and the Role of Synoviocytes as Biological Key.

The purpose of this study was to investigate the influence of moderate physical activity (MPA) on the expression of osteoarthritis (OA)-related (IL-1ß, IL-6, TNF-α, MMP-13) and anti-inflammatory and chondroprotective (IL-4, IL-10, lubricin) biomarkers in the synovium of an OA-induced rat model. A total of 32 rats were divided into four groups: Control rats (Group 1); rats performing MPA (Group 2); anterior cruciate ligament transection (ACLT)-rats with OA (Group 3); and, ACLT-rats performing MPA (Group 4). Analyses were performed using Hematoxylin & Eosin (H & E) staining, histomorphometry and immunohistochemistry. In Group 3, OA biomarkers were significantly increased, whereas, IL-4, IL-10, and lubricin were significantly lower than in the other experimental groups. We hypothesize that MPA might partake in rescuing type B synoviocyte dysfunction at the early stages of OA, delaying the progression of the disease.

An Overview of the Pathogenesis and Treatment of Elbow Osteoarthritis.

The elbow joint could be associated with degenerative processes of primary and post-traumatic aetiology. Among these, osteoarthritis may also be secondary to repeated use as well as trauma. Pain, discomfort and progressive loss of functionality are common signs of this condition. The evaluation of elbow osteoarthritis should comprise an in-depth study to detect the primary cause of the illness and to facilitate the decision-making process regarding personalized treatment. Discordance between clinical manifestations and radiological findings is common. Conservative approaches may provide symptomatic relief in the early stages of disease for most patients. The goal of the treatment is to reduce pain and ensure an adequate range of motion and proper functioning of the joint while preserving the anatomical structure, to postpone elbow arthroplasty interventions for as long as possible. According to treatment guidelines, surgery should be considered depending on aetiology and severity, patient age, and functional demands. This narrative review aims to investigate the current literature regarding the pathogenesis and treatment of primary and post-traumatic arthritis of the elbow.

Combining agent based-models and virtual screening techniques to predict the best citrus-derived vaccine adjuvants against human papilloma virus.

BACKGROUND: Human papillomavirus infection is a global social burden that, every year, leads to thousands new diagnosis of cancer. The introduction of a protocol of immunization, with Gardasil and Cervarix vaccines, has radically changed the way this infection easily spreads among people. Even though vaccination is only preventive and not therapeutic, it is a strong tool capable to avoid the consequences that this pathogen could cause. Gardasil vaccine is not free from side effects and the duration of immunity is not always well determined. This work aim to enhance the effects of the vaccination by using a new class of adjuvants and a different administration protocol. Due to their minimum side effects, their easy extraction, their low production costs and their proven immune stimulating activity, citrus-derived molecules are valid candidates to be administered as adjuvants in a vaccine formulation against Hpv. RESULTS: With the aim to get a stronger immune response against Hpv infection we built an in silico model that delivers a way to predict the best adjuvants and the optimal means of administration to obtain such a goal. Simulations envisaged that the use of Neohesperidin elicited a strong immune response that was then validated in vivo. CONCLUSIONS: We built up a computational infrastructure made by a virtual screening approach able to preselect promising citrus derived compounds, and by an agent based model that reproduces HPV dynamics subject to vaccine stimulation. This integrated methodology was able to predict the best protocol that confers a very good immune response against HPV infection. We finally tested the in silico results through in vivo experiments on mice, finding good agreement.