Study Design.: In vitro study. Objective.: To investigate the effect of irisin on human nucleus pulposus cells (hNPCs) in vitro. Summary of Background Data.: Physical exercise (PE) favours weight loss and ameliorates function in patients with low back pain. Although there is no biological evidence that the intervertebral disk (IVD) can respond to PE, recent studies have shown that running is associated with increased IVD hydration and hypertrophy. Irisin, a myokine released upon muscle contraction, has demonstrated anabolic effects on different cell types, including chondrocytes. Materials and Methods.: hNPCs were exposed to 5, 10, and 25 ng/mL irisin. Cell proliferation, glycosaminoglycan (GAG) content, metabolic activity, gene expression of collagen type II (COL2), matrix metalloproteinase (MMP)-13, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-3, aggrecan (ACAN), interleukin (IL)-1β, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 were assessed. In addition, MTT assay and ADAMTS-5, COL2, TIMP-1, and IL-1β gene expression were evaluated following incubation with irisin for 24 hours and subsequent culture with 10 ng/mL IL-1β and vice versa (incubation for 24 hours with IL-1β and subsequent culture with irisin). Results.: Irisin increased hNPC proliferation, metabolic activity, and GAG content, as well as COL2, ACAN, TIMP-1 and TIMP-3 gene expression, while decreasing MMP-13 and IL-1β mRNA levels. Irisin pretreatment of hNPCs cultured in proinflammatory conditions resulted in a rescue of metabolic activity and a decrease of IL-1β levels. Similarly, incubation of hNPCs with IL-1β and subsequent exposure to irisin led to an increment of metabolic activity, COL2 gene expression, and a reduction of IL-1β and ADAMTS-5 levels. Conclusions.: Irisin increases hNPC proliferation, GAG content, metabolic activity, and promotes anabolic gene expression while reducing catabolic markers. Irisin may be one of the mediators by which PE and muscle tissues modulate IVD metabolism, suggesting the existence of a biological cross-talk between the muscle and IVD.

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.

WHARTON'S JELLY MSCS-DERIVED EXOSOMES AS CELL-FREE THERAPEUTIC STRATEGY FOR INTERVERTEBRAL DISC REGENERATION

ANTI-INFLAMMATORY EFFECTS OF PRECONDITIONED BONE MARROW MSC-DERIVED SECRETOME ON DEGENERATED HUMAN NUCLEUS PULPOSUS CELLS IN VITRO

Biomarkers are becoming pivotal in understanding the complex pathophysiology of disc herniation and guiding novel therapeutic strategies. Recent research highlights the value of molecular and cellular biomarkers in delineating disease progression, treatment monitoring and patient stratification. This review summarizes current advances in the identification and validation of emerging biomarkers across genomic, transcriptomic, proteomic, and metabolomic domains, emphasizing their potential to bridge basic mechanistic insights with clinical translation. Particular attention is given to the interplay between inflammatory mediators, extracellular matrix turnover, and immune cell activity as indicators of lumbar disc herniation diagnosis and prognosis. Despite encouraging progress, standardization of biomarker validation protocols, inter-study comparability, and large-scale clinical implementation remain major challenges. Future directions include the integration of multi-omics technologies and bioinformatic tools to identify predictive biomarker panels with diagnostic and prognostic utility towards personalized medicine.