Osteoarthritis (OA) is a chronic progressive disease of the joint. Although representing the most frequent cause of disability in the elderly, OA remains partly obscure in its pathogenic mechanisms and is still the orphan of resolutive therapies. The concept of what was once considered a “wear and tear” of articular cartilage is now that of an inflammation-related disease that affects over time the whole joint. The attention is increasingly focused on the synovium. Even from the earliest clinical stages, synovial inflammation (or synovitis) is a crucial factor involved in OA progression and a major player in pain onset. The release of inflammatory molecules in the synovium mediates disease progression and worsening of clinical features. The activation of synovial tissue-resident cells recalls innate immunity cells from the bloodstream, creating a proinflammatory milieu that fuels and maintains a damaging condition of low-grade inflammation in the joint. In such a context, cellular and molecular inflammatory behaviors in the synovium could be the primum movens of the structural and functional alterations of the whole joint. This paper focuses on and discusses the involvement of innate immunity cells in synovitis and their role in the progression of OA.

In osteoarthritis (OA), an inflammatory environment is responsible for the imbalance between the anabolic and catabolic activity of chondrocytes and, thus, for articular cartilage derangement. This study was aimed at providing further insight into the impairment of the anabolic cytokine IL-4 and its receptors in human OA cartilage, as well as the potential ability of IL-4 to antagonize the catabolic phenotype induced by IL-1β. The in vivo expression of IL-4 and IL-4 receptor subunits (IL-4R, IL-2Rγ, IL-13Rα1) was investigated on full thickness OA or normal knee cartilage. IL-4 expression was found to be significantly lower in OA, both in terms of the percentage of positive cells and the amount of signal per cell. IL-4 receptor type I and II were mostly expressed in mid-deep cartilage layers. No significant difference for each IL-4 receptor subunit was noted. IL-4 anti-inflammatory and anti-catabolic activity was assessed in vitro in the presence of IL-1β and/or IL-4 for 24 hours using differentiated high density primary OA chondrocyte also exhibiting the three IL-4 R subunits found in vivo. Chemokines, extracellular matrix degrading enzymes and their inhibitors were evaluated at mRNA (real time PCR) and protein (ELISA or western blot) levels. IL-4 did not affect IL-1β-induced mRNA expression of GRO-α/CXCL1, IL-8/CXCL8, ADAMTS-5, TIMP-1 or TIMP-3. Conversely, IL-4 significantly inhibited RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, MMP-13 and ADAMTS-4. These results were confirmed at protein level for RANTES/CCL5 and MMP-13. Our results indicate for the first time that OA cartilage has a significantly lower expression of IL-4. Furthermore, we found differences in the spectrum of biological effects of IL-4. The findings that IL-4 has the ability to hamper the IL-1β-induced release of both MMP-13 and CCL5/RANTES, both markers of OA chondrocytes, strongly indicates IL-4 as a pivotal anabolic cytokine in cartilage whose impairment impacts on OA pathogenesis.

This work aims to describe the development and validation of two low-intensity pulsed ultrasound stimulation systems able to control the dose delivered to the biological target. Transducer characterization was performed in terms of pressure field shape and intensity, for a high-frequency range (500 kHz to 5 MHz) and for a low-frequency value (38 kHz). This allowed defining the distance, on the beam axis, at which biological samples should be placed during stimulation and to exactly know the intensity at the target. Carefully designed retaining systems were developed, for hosting biological samples. Sealing tests proved their impermeability to external contaminants. The assembly/de-assembly time of the systems resulted ~3 min. Time-domain acoustic simulations allowed to precisely estimate the ultrasound beam within the biological sample chamber, thus enabling the possibility to precisely control the pressure to be transmitted to the biological target, by modulating the transducer's input voltage. Biological in vitro tests were also carried out, demonstrating the sterility of the system and the absence of toxic and inflammatory effects on growing cells after multiple immersions in water, over seven days.

Objectives: To investigate the clinical associations of hand osteoarthritis (HOA) and their relationships with radiographic features. Methods: A total of 446 patients with hand osteoarthritis (HOA; 233 with erosive HOA (EHOA) and 213 with non-EHOA) and 307 controls were evaluated. Demographic and clinical data from patients and controls were recorded based on medical records/clinical reports and an anamnesis of drug consumption. Posteroanterior radiographs of both hands were obtained from all HOA patients and were assessed using the Kellgren and Lawrence (K&L) and Kallman scoring systems. Results: After adjustment for age, gender, and body mass index (BMI), HOA patients showed a significantly increased odds ratio (OR) for hypercholesterolaemia [OR 2.10, 95% confidence interval (CI) 1.39–3.16, p < 0.0005] and autoimmune thyroiditis (OR 4.85, 95% CI 1.77–13.29, p = 0.002), as well as for knee (OR 1.63, 95% CI 1.09–2.44, p = 0.018) and hip OA (OR 1.87, 95% CI 1.07–3.27, p = 0.029). No significant increase for systemic hypertension, ischaemic heart disease, and diabetes mellitus was found. Patients with EHOA and non-EHOA showed similar risks for the above-mentioned co-morbidities. A similar occurrence of clinical associations was also observed in patients with HOA alone and in those with generalized OA. No association between radiographic scores and clinical associations was observed. Conclusions: Patients with HOA present a direct association with hypercholesterolaemia (and autoimmune thyroiditis) but do not show increased ischaemic cardiovascular manifestations compared to controls. No significant association between radiographic scores and co-morbidities was found.