The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models.

Pure Platelet and Leukocyte-Platelet-Rich Plasma for Regenerative Medicine in Orthopedics-Time- and Preparation-Dependent Release of Growth Factors and Effects on Synovial Fibroblasts: A Comparative Analysis.

Intra-articular injections of autologous platelet concentrates are considered capable to enhance the healing of cartilage lesions, alleviate joint inflammation, and relieve other musculoskeletal pathological conditions. The aim of this study was to analyze the soluble fractions obtained from platelet-rich plasma (pure- and leukocyte-PRP) to compare time- and preparation-dependent modifications of growth factor concentrations and the supporting activity of the two preparations on synovial fibroblast growth and hyaluronic acid (HA) production in vitro. The release kinetics of FGF-2, SDF-1, VEGF, HGF, EGF, PD GF-AB/BB, IGF-1, VCAM-1, and TGF-β isoforms were followed up to 168 h after PRP activation, and their amounts were determined by multiplex-beads immunoassay.

Mesenchymal stromal cells from a progressive pseudorheumatoid dysplasia patient show altered osteogenic differentiation.

Background: Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory skeletal disease with childhood onset and is characterized by a progressive chondropathy in multiple joints, and skeletal abnormalities. To date, the etiopathological relationship between biological modification occurring in PPRD and genetic mutation remains an open issue, partially due to the limited availability of biological samples obtained from PPRD patients for experimental studies.

Case Presentation: We describe the clinical features of a PPRD patient and experimental results obtained from the biological characterization of PPRD mesenchymal stromal cells (MSCs) and osteoblasts (OBs) compared to normal cell populations.

Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes.

Notch signaling has been identified as a critical regulator of cartilage development and homeostasis. Its pivotal role was established by both several joint specific Notch signaling loss of function mouse models and transient or sustained overexpression. NOTCH1 is the most abundantly expressed NOTCH receptors in normal cartilage and its expression increases in osteoarthritis (OA), when chondrocytes exit from their healthy "maturation arrested state" and resume their natural route of proliferation, hypertrophy, and terminal differentiation.

Biomechanical-Based Protocol for Study of Cartilage Response to Cyclic Loading: A Proof-of-Concept in Knee Osteoarthritis.

Osteoarthritis (OA) is an evolving disease and a major cause of pain and impaired mobility. A deeper understanding of cartilage metabolism in response to loading is critical to achieve greater insight into OA mechanisms. While physiological joint loading helps maintain cartilage integrity, reduced or excessive loading have catabolic effects.

Oxidative stress-induced DNA damage and repair in primary human osteoarthritis chondrocytes: focus on IKKα and the DNA Mismatch Repair System.

During osteoarthritis development, chondrocytes are subjected to a functional derangement. This increases their susceptibility to stressful conditions such as oxidative stress, a characteristic of the aging tissue, which can further provoke extrinsic senescence by DNA damage responses. It was previously observed that IκB kinase α knockdown increases the replicative potential of primary human OA chondrocytes cultured in monolayer and the survival of the same cells undergoing hypertrophic-like differentiation in 3-D.

Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role.

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients' quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix.

Long-Term Follow-up of a Randomized Study of Oral Etoposide versus Fermentatum Pini as Maintenance Therapy in Osteosarcoma Patients in Complete Surgical Remission after Second Relapse.

Background: In relapsed osteosarcoma, the 5-yr postrelapse disease-free survival (PRDFS) rate after the second relapse is <20%. In June 2007, a randomized study was started comparing oral etoposide vs fermentatum Pini (an extract derived from the parasitic plant L., European mistletoe) as maintenance therapy in patients with metastatic osteosarcoma in complete surgical remission after the second relapse.

Release kinetic of pro- and anti-inflammatory biomolecules from platelet-rich plasma and functional study on osteoarthritis synovial fibroblasts.

Background Aims: This study evaluated the release kinetics of numerous representative and less studied platelet-rich plasma (PRP) cytokines/chemokines with regard to the effects of various cellular compositions and incubation times. In addition, the biological effects of different PRPs on osteoarthritis synovial fibroblasts in vitro were tested.

Methods: Peripheral whole blood was collected from healthy donors, and pure platelet-rich plasma (P-PRP), leukocyte-rich platelet-rich plasma (L-PRP) and platelet-poor plasma (PPP) were prepared for the analysis of the following biomolecules: IL-1β, IL-4, IL-6, IL-10, IL-17a, IL-22, MIP-1α/CCL-3, RANTES/CCL-5, MCP-3/CCL-7, Gro-α/CXCL-1, PF-4/CXCL-4, ENA-78/CXCL-5, NAP-2/CXCL-7, IL-8/CXCL-8, Fractalkine/CX3CL-1, s-CD40L P-PRP, L-PRP and PPP.

Platelet Concentrates in Musculoskeletal Medicine.

Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.

Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components.

Mechanical stimulation appears to play a key role in cartilage homeostasis maintenance, but it can also contribute to osteoarthritis (OA) pathogenesis. Accumulating evidence suggests that cartilage loading in the physiological range contributes to tissue integrity maintenance, whereas excessive or reduced loading have catabolic effects. However, how mechanical stimuli can regulate joint homeostasis is still not completely elucidated and few data are available on human cartilage.

Chitosan-based scaffold counteracts hypertrophic and fibrotic markers in chondrogenic differentiated mesenchymal stromal cells.

Cartilage tissue engineering remains problematic because no systems are able to induce signals that contribute to native cartilage structure formation. Therefore, we tested the potentiality of gelatin-polyethylene glycol scaffolds containing three different concentrations of chitosan (CH; 0%, 8%, and 16%) on chondrogenic differentiation of human platelet lysate-expanded human bone marrow mesenchymal stromal cells (hBM-MSCs). Typical chondrogenic (SOX9, collagen type 2, and aggrecan), hypertrophic (collagen type 10), and fibrotic (collagen type 1) markers were evaluated at gene and protein level at Days 1, 28, and 48.

Biomaterials: Foreign Bodies or Tuners for the Immune Response?

The perspectives of regenerative medicine are still severely hampered by the host response to biomaterial implantation, despite the robustness of technologies that hold the promise to recover the functionality of damaged organs and tissues. In this scenario, the cellular and molecular events that decide on implant success and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. To avoid adverse events, rather than the use of inert scaffolds, current state of the art points to the use of immunomodulatory biomaterials and their knowledge-based use to reduce neutrophil activation, and optimize M1 to M2 macrophage polarization, Th1 to Th2 lymphocyte switch, and Treg induction.

Cartilage and Bone Serum Biomarkers as Novel Tools for Monitoring Knee Osteochondritis Dissecans Treated with Osteochondral Scaffold.

Knee osteochondritis dissecans (OCD) is a focal disease of the joint characterized by modifications of bone and cartilage tissues. Biomimetic osteochondral scaffolds are used to restore these tissues. The aim of this prognostic prospective cohort study was to evaluate serum biomarkers of cartilage (fragments or propeptide of type II collagen: CTXII, C2C, and CPII) and bone (tartrate-resistant acid phosphatase (TRAP) 5b and osteocalcin (OC)) turnover during follow-up of patients treated with an osteochondral scaffold, to identify which were related to healing outcome and clinical score.

Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects.

An age-related dysregulation of immune response, known as immunosenescence, contributes to increased susceptibility to infections, frailty and high risk of mortality in the elderly. Torquetenovirus (TTV), a circular, single-stranded DNA virus, is highly prevalent in the general population and it may persist in the organism, also in association with other viruses such as cytomegalovirus (CMV), causing chronic viremia. The relationship that TTV establishes with the immune system of infected hosts is not clear.

Effect of microfragmented adipose tissue on osteoarthritic synovial macrophage factors.

Cell-based therapies using adipose-derived mesenchymal stromal cells (ADMSCs) have shown promising results for the treatment of osteoarthritis (OA). In fact, ADMSCs are now indicated as one of the most powerful cell sources through their immunomodulatory and anti-inflammatory activities. Recently, an innovative one-step closed device was developed to obtain microfragmented adipose tissue (MF) to avoid the need for good manufacturing practices for ADMSCs expansion while maintaining their regenerative potential.

Clinical and Biological Signature of Osteochondritis Dissecans in a Cross-Sectional Study.

The healing potential of knee osteochondritis dissecans (OCD) focal lesions is not well defined. We performed a cross-sectional study correlating local and systemic biological characteristics with the patients' characteristics. We evaluated both local tissue markers (CD34, CD146, CD166, and tartrate-resistant acid phosphatase (TRAP)) and systemic serum biomarkers (fragments or propeptide of type II collagen: C2C, CTX-II, CPII, and TRAP5b) on histologically scored osteochondral fragments or serum from OCD patients.

Focal Defects of the Knee Articular Surface: Evidence of a Regenerative Potential Pattern in Osteochondritis Dissecans and Degenerative Lesions.

The surgical treatment of knee articular focal lesions may offer heterogeneous clinical results. Osteochondritis dissecans (OCD) lesions showed to heal better than degenerative lesions (DL) but the underlying biological reasons are unknown. We evaluated the basal histological and immunohistochemical characteristics of these lesions analyzing a series of osteochondral fragments from young patients with similar age but presenting different etiology.

Repair Potential of Matrix-Induced Bone Marrow Aspirate Concentrate and Matrix-Induced Autologous Chondrocyte Implantation for Talar Osteochondral Repair: Patterns of Some Catabolic, Inflammatory, and Pain Mediators.

Objective: The low regenerative potential of cartilage contributed to the development of different cell therapies aimed to improve the clinical outcome in young patients with Osteochondral Lesions of the Talus (OLT). This study is designed to assess the regenerative potential of autologous matrix-induced Bone Marrow Aspirate Concentrate (mBMAC) and matrix-induced Autologous Chondrocyte Implantation (mACI) evaluating, on a small number of osteochondral biopsies, the expression of some catabolic, inflammatory, and pain mediators.

Design: Twenty-two patients with OLT were analyzed in this study; 7 were treated with mACI and 15 with mBMAC.

Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules.

Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl, 10% of autologous thrombin, 10% of a mixture of CaCl + thrombin, and 10% of collagen type I.