Physical exercise favors weight loss and ameliorates articular pain and function in patients suffering from osteoarthritis. Irisin, a myokine released upon muscle contraction, has demonstrated to yield anabolic effects on different cell types. This study aimed to investigate the effect of irisin on human osteoarthritic chondrocytes (hOAC) in vitro. Our hypothesis was that irisin would improve hOAC metabolism and proliferation. Cells were cultured in growing media and then exposed to either phosphate-buffered saline (control group) or human recombinant irisin (experimental group). Cell proliferation, glycosaminoglycan content, type II/X collagen gene expression and protein quantification as well as p38/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK), protein kinase B (Akt), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) involvement were evaluated. Furthermore, gene expression of interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 were investigated following irisin exposure. Irisin increased hOAC cell content and both type II collagen gene expression and protein levels, while decreased type X collagen gene expression and protein levels. Moreover, irisin decreased IL-1, IL-6, MMP-1, MMP-13 and iNOS gene expression, while increased TIMP-1 and TIMP-3 levels. These effects seemed to be mediated by inhibition of p38, Akt, JNK and NFκB signaling pathways. The present study suggested that irisin may stimulate hOAC proliferation and anabolism inhibiting catabolism through p38, Akt, JNK, and NFκB inactivation in vitro, demonstrating the existence of a cross-talk between muscle and cartilage.

Knee septic arthritis is a devastating complication following anterior cruciate ligament (ACL) reconstruction. To prevent this issue, intraoperative soaking of ACL grafts with vancomycin is often performed before implantation. Although vancomycin cytotoxicity has been reported several times, little is known about its biological effect on tenocytes. The aim of this study was to evaluate the in vitro effects of vancomycin on human primary tenocytes (hTCs). hTCs were isolated from hamstring grafts of four patients undergoing ACL reconstruction. After expansion, hTCs were treated with different concentrations of vancomycin (0, 2.5, 5, 10, 25, 50 and 100 mg/mL) for 10, 15, 30 and 60 min. In vitro cytotoxicity was evaluated measuring metabolic activity, cell toxicity, and apoptosis. hTC metabolic activity was affected starting from 10 mg/mL vancomycin and decreased markedly at 100 mg/mL. Cell viability remained unaffected only at a concentration of 2.5 mg/mL vancomycin. Vancomycin cytotoxicity was detected from 10 mg/mL after 15 min and at all higher concentrations. Cells died when treated with concentrations higher than 5 mg/mL. The use of this antibiotic on tendons to prevent infections could be useful and safe for resident cells if used at a concentration of 2.5 mg/mL for up to 1 h of treatment.

Low back pain (LBP) is one of the most frequent symptoms associated with intervertebral disc degeneration (IDD) and affects more than 80% of the population, with strong psychosocial and economic impacts. The main cause of IDD is a reduction in the proteoglycan content within the nucleus pulposus (NP), eventually leading to the loss of disc hydration, microarchitecture, biochemical and mechanical properties. The use of mesenchymal stem cells (MSCs) has recently arisen as a promising therapy for IDD. According to numerous reports, MSCs mediate their regenerative and immunomodulatory effects mainly through paracrine mechanisms. Recent studies have suggested that extracellular vesicles (EVs) extracted from MSCs may be a promising alternative to cell therapy in regenerative medicine. EVs, including exosomes and microvesicles, are secreted by almost all cell types and have a fundamental role in intercellular communication. Early results have demonstrated the therapeutic potential of MSCs-derived EVs for the treatment of IDD through the promotion of tissue regeneration, cell proliferation, reduction in apoptosis and modulation of the inflammatory response. The aim of this review is to focus on the biological properties, function, and regulatory properties of different signaling pathways of MSCs-derived exosomes, highlighting their potential applicability as an alternative cell-free therapy for IDD.

Background: Irisin, a myokine secreted during physical activity, has garnered attention for its potential roles in cartilage homeostasis and musculoskeletal health. Whole-body electromyostimulation (WB-EMS) is an emerging exercise modality that enhances muscle recruitment and may stimulate greater irisin release. This study aimed to compare the acute serum irisin response following aerobic exercise with and without WB-EMS in healthy individuals. Methods: A total of 24 healthy adults were enrolled and randomized to undergo either aerobic physical activity (PA) or WB-EMS (n = 12 each). Both groups performed identical exercise routines, with the WB-EMS group additionally receiving muscle stimulation via a standardized protocol. Serum irisin levels were measured at baseline (T0), 10 minutes post-exercise (T1), and 1 hour post-exercise (T2) using ELISA. Statistical analysis was performed using two-way ANOVA with post hoc testing. Results: At T1, serum irisin levels did not significantly differ from baseline in either group. At T2, the WB-EMS group demonstrated a statistically significant increase in irisin levels compared to both T0 and T1 (p < 0.01), as well as to the PA group (p < 0.01). In contrast, the PA group showed only a slight, non-significant rise at T2. These findings suggest that WB-EMS induces a more robust irisin response than traditional aerobic exercise. Conclusions: WB-EMS appears to enhance irisin release in healthy individuals following acute exercise. These results support further research into WB-EMS as a novel strategy to modulate myokine production with potential therapeutic relevance in musculoskeletal conditions such as osteoarthritis.

Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive joint degeneration driven by extracellular matrix (ECM) breakdown, chondrocyte apoptosis, and chronic low-grade inflammation. Despite the availability of several pharmacological and non-pharmacological interventions, no current therapy effectively halts or reverses disease progression. Physical activity is traditionally recognized as a cornerstone in OA management, improving pain and functional outcomes; however, the molecular mechanisms underlying its beneficial effects remain partially understood. Irisin, a myokine generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 in response to muscle contraction, has recently emerged as a potential regulator of cartilage homeostasis. Experimental evidence indicates that irisin exerts pleiotropic effects by modulating inflammatory and catabolic signaling pathways, promoting anabolic and reparative processes, restoring autophagic and mitophagic flux, and preserving mitochondrial function. These actions collectively contribute to the maintenance of ECM integrity and chondrocyte viability. In vitro and in vivo studies consistently support the protective role of irisin in cartilage biology, highlighting its involvement in the muscle–cartilage axis and its potential as both a biomarker and therapeutic target for OA. This narrative review critically evaluates the chondrocyte-specific mechanisms, receptor uncertainties, experimental-model limitations, analytical challenges, and delivery strategies that currently define the biological and translational relevance of irisin in OA. Particular attention is given to the identification of irisin-mediated signaling pathways in chondrocytes, optimization of delivery strategies, and the definition of exercise regimens capable of maximizing its chondroprotective effects.

THE MYOKINE IRISIN INHIBITS TENOCYTE INFLAMMATION IN VITRO