Knee osteoarthritis (KOA) is a progressive and chronic musculoskeletal condition that continues to be the leading cause of disability worldwide. Conventional treatment approaches for the management of KOA largely focus on symptom alleviation rather than halting or reversing disease progression. However, recent advancements have highlighted the integrated interplay of mechanical stress, inflammation, cellular senescence, and chondrocyte dysfunction in the progression of KOA, in turn prompting new therapeutic strategies. Therefore, emerging interventions such as regenerative medicine, gene therapy, senolytic, platelet-rich plasma (PRP), disease-modifying osteoarthritis drugs (DMODs), and biologics have broadened the therapeutic options. Additionally, natural compounds demonstrated potential in KOA treatment with promising chondroprotective and anti-inflammatory effects.Moreover, digital technologies and clinical and molecular phenotyping enhanced early diagnosis, monitoring, and personalized management of the disease. Therefore, the current narrative review focuses on the molecular insights, clinical outcomes and prospects for the rapidly evolving landscape of current and emerging treatment approaches for the management of knee osteoarthritis (KOA).

Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.

Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.

In this study, we investigated the effects of the flavonoid galangin on the expression of the mucin 5AC (MUC5AC) gene in airway cells. Human pulmonary epithelial NCI-H292 cells were pretreated with galangin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. We also examined the effects of galangin on the PMA-induced nuclear factor-κB (NF-κB) signaling pathway. Galangin inhibited the production of glycoproteins and the expression of MUC5AC mRNA induced by PMA via prevention of NF-κB inhibitor α degradation and NF-κB p65 nuclear translocation. These findings indicated that galangin suppressed mucin gene expression by modulating the NF-κB signaling pathway in human pulmonary epithelial cells.

This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.

Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.

In this study, we investigated the effects of the flavonoid galangin on the expression of the mucin 5AC (MUC5AC) gene in airway cells. Human pulmonary epithelial NCI-H292 cells were pretreated with galangin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. We also examined the effects of galangin on the PMA-induced nuclear factor-κB (NF-κB) signaling pathway. Galangin inhibited the production of glycoproteins and the expression of MUC5AC mRNA induced by PMA via prevention of NF-κB inhibitor α degradation and NF-κB p65 nuclear translocation. These findings indicated that galangin suppressed mucin gene expression by modulating the NF-κB signaling pathway in human pulmonary epithelial cells.

This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.

Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.

In this study, we investigated the effects of the flavonoid galangin on the expression of the mucin 5AC (MUC5AC) gene in airway cells. Human pulmonary epithelial NCI-H292 cells were pretreated with galangin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. We also examined the effects of galangin on the PMA-induced nuclear factor-κB (NF-κB) signaling pathway. Galangin inhibited the production of glycoproteins and the expression of MUC5AC mRNA induced by PMA via prevention of NF-κB inhibitor α degradation and NF-κB p65 nuclear translocation. These findings indicated that galangin suppressed mucin gene expression by modulating the NF-κB signaling pathway in human pulmonary epithelial cells.