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Abstract Background Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention. Methods To simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC’s therapeutic effects on chondrocytes. Results The results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1β, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA. Conclusions This study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC’s comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC’s therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.

BackgroundChondrocytes are the primary cells responsible for maintaining cartilage integrity and function. Their role in cartilage homeostasis and response to inflammation is crucial for understanding the progression and potential therapeutic interventions for various cartilage-related disorders. Developing an accessible and cost-effective model to generate viable chondrocytes and to assess their response to different bioactive compounds can significantly advance our knowledge of cartilage biology and contribute to the discovery of novel therapeutic approaches. ObjectiveWe developed a novel, streamlined protocol for generating chondrocytes from bone marrow–derived mesenchymal stem cells (BMSCs) in a 3D culture system that offers significant implications for the study of cartilage biology and the discovery of potential therapeutic interventions for cartilage-related and associated disorders. MethodsWe developed a streamlined protocol for generating chondrocytes from BMSCs in a 3D culture system using an “in-tube” culture approach. This simple pellet-based 3D culture system allows for cell aggregation and spheroid formation, facilitating cell-cell and cell–extracellular matrix interactions that better mimic the in vivo cellular environment compared with 2D monolayer cultures. A proinflammatory chondrocyte model was created by treating the chondrocytes with lipopolysaccharide and was subsequently used to evaluate the anti-inflammatory effects of vitamin D, curcumin, and resveratrol. ResultsThe established protocol successfully generated a large quantity of viable chondrocytes, characterized by alcian blue and toluidine blue staining, and demonstrated versatility in assessing the anti-inflammatory effects of various bioactive compounds. The chondrocytes exhibited reduced inflammation, as evidenced by the decreased tumor necrosis factor-α levels, in response to vitamin D, curcumin, and resveratrol treatment. ConclusionsOur novel protocol offers an accessible and cost-effective approach for generating chondrocytes from BMSCs and for evaluating potential therapeutic leads in the context of inflammatory chondrocyte–related diseases. Although our approach has several advantages, further investigation is required to address its limitations, such as the potential differences between chondrocytes generated using our protocol and those derived from other established methods, and to refine the model for broader applicability and clinical translation.

Turmeric is a plant with a very long history of medicinal use across different cultures. Curcumin is the active part of turmeric, which has exhibited various beneficial physiological and pharmacological effects. This review aims to critically appraise the corpus of literature associated with the above pharmacological properties of curcumin, with a specific focus on antioxidant, anti-inflammatory, anticancer and antimicrobial properties. We have also reviewed the different extraction strategies currently in practice, highlighting the strengths and drawbacks of each technique. Further, our review also summarizes the clinical trials that have been conducted with curcumin, which will allow the reader to get a quick insight into the disease/patient population of interest with the outcome that was investigated. Lastly, we have also highlighted the research areas that need to be further scrutinized to better grasp curcumin’s beneficial physiological and medicinal properties, which can then be translated to facilitate the design of better bioactive therapeutic leads.

Human dental pulp stem cells (hDPSCs) are promising source of cells for numerous and varied regenerative medicine applications as those possess high proliferation potential with multilineage differentiation capacity compare to other sources of adult stem cells; therefore, hDPSCs could be the good source for autologous transplantation in tissue engineering and regenerative medicine. In this study stem cells were isolated from dental pulp and were characterised by flowcytometry and immunocytochemistry. The controlled cells as well as, 7-day cultured cells were positive for transcription factors, OCT 4 and SOX 2 thatconfirmed isolated cellsasmesenchymal stem cells (MSCs). These cells showed positive expression for CD 19, CD 73, CD 90, CD 105 and are negative for CD 34, CD 45. Viability of hDPSCS were studied by trypan blue (TB) staining and fluorescent microscopic study. After 7 days of passaging by using several growth factors, cells express neural cell markers oligodendrocyte and glial fibrillary acidic protein. Specifically, osteocytes were grown from dental pulp MSCSsin vitro with the help of growth factors, dexamethasone, ascorbic acid-2- phosphate and β-glycerophosphate whereas, adipocytes were grown with indomethacin, 3-isobutyl-1-methylxanthine and insulin. Osteocytes and adipocytes were characterized by von Kossa and Oil red O staining, respectively. Chromosomal analysis of dental pulp-MSCs was done for qualitative assessment of MSCs. Karyotyping indicated diploid chromosome number in dental pulp derived MSCs. In vitro grown osteocytes could be used for bone fracture reunion cases, and adipocytes could be used for further research purposes.