Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management.

Inflammation and apoptosis are interrelated biological processes that have a significant impact on the advancement and growth of certain chronic diseases, such as cardiovascular problems, neurological conditions, and osteoarthritis. Recent research has emphasized that focusing on these mechanisms could result in novel therapeutic approaches that aim to decrease the severity of diseases and enhance patient outcomes. Hydroxytyrosol (HT), which is well-known for its ability to prevent oxidation, has been identified as a possible candidate for regulating both inflammation and apoptosis. In this review, we will highlight the multifaceted benefits of HT as a therapeutic agent in mitigating inflammation, apoptosis, and associated conditions. This review provides a comprehensive overview of the latest in vitro and in vivo research on the anti-inflammatory and antiapoptotic effects of HT and the mechanisms by which it works. Based on these studies, it is strongly advised to use HT as a bioactive ingredient in pharmaceutical products intended for mitigating inflammation, as well as those with apoptosis applications.

Osteoarthritis (OA) presents a significant therapeutic challenge, necessitating innovative biomaterial strategies to reduce chronic inflammation and promote cartilage regeneration. This study developed a hybrid gelatine (GE)/polyvinyl alcohol (PVA) hydrogel crosslinked with genipin (GNP) to effectively deliver Hydroxytyrosol (HT). A 6% GE was incorporated with 3% and 5% PVA concentrations, followed by 0.1% (w/v) GNP. The physicochemical and biocompatibility properties were further evaluated. Physicochemical analysis identified the GPVA5%-GNP formulation as optimal, featuring an interconnected porous structure, optimal swelling ratio (640.43 ± 22.28%), improved hydrophilicity (44.50 ± 1.81°), controlled biodegradation, and enhanced compressive strength (96.88 ± 0.72%). Chemical tests confirmed thermal and structural stability, while biocompatibility assays showed over 95% cell viability. The therapeutic potential was evaluated using an IL-1β-induced inflammatory model in human chondrocytes. MTT assays revealed that HT at 12.5, 25, and 50 μM restored metabolic activity in a dose-dependent manner over 14 days, outperforming the 9 μM Glucosamine Sulphate positive control. The 50 μM HT dose yielded the best metabolic recovery, supported by Live/Dead imaging that showed increased viable cell density from Day 1 to Day 7. Overall, the GPVA5%-GNP hydrogel loaded with 50 μM HT offers a robust protective environment that reduces catabolic stress and promotes cell proliferation, making it a promising localized therapy for cartilage regeneration in OA.