Background: Intervertebral disc degeneration (IDD) is a progressive age‐related disorder characterized by the reduction in the number of nucleus pulposus cells (NPCs) and degradation of extracellular matrix (ECM), thereby leading to chronic pain and disability. The pathogenesis of IDD is multifaceted, and current therapeutic strategies remain limited. The nucleus pulposus (NP), primarily composed of NPCs, proteoglycans, and type II collagen, constitutes essential components for maintaining intervertebral disc (IVD) function and spinal motion. The disturbed homeostasis of NPCs is closely associated with IDD. Accumulating evidence increasingly suggests the crucial role of programmed cell death (PCD) in regulating the homeostasis of NPCs.Aims: This review aimed to elucidate various forms of PCD and their respective roles in IDD, and investigate diverse strategies targeting the cell death of NPCs for IDD treatment.Materials & Methods: We collected the relevant literature regarding PCD and their roles in the development of IDD. Subsequently, we comprehensively summarized the intricate association between PCD and IDD, and also explored the potential and application of cell therapy and traditional Chinese medicine (TCM) in the prevention and treatment of IDD.Results: Current literature indicated that the PCD of NPCs was closely associated with the pathogenesis of IDD. Additionally, the development of targeted pharmaceuticals based on the mechanisms of PCD could effectively impede the loss of NPCs.Conclusion: This review demonstrated that targeting the PCD of NPCs may be a promising strategy for the treatment of IDD.

Background: Osteoarthritis is the most prevalent joint disorder, and osteoarthritis associated with high BMI contributes significantly to the global disease burden. The aim of this study is to elucidate the burden of BMI-related osteoarthritis and to investigate the causal relationship between varying degrees of obesity and osteoarthritis. Methods: The Global Burden of Disease (GBD) 2021 study was used to conduct an epidemiological analysis of osteoarthritis. This included descriptive statistics, age–sex differences, Joinpoint regression analysis, burden sources and control measures, and projections up to 2050. A two-sample Mendelian randomization analysis was also performed to explore the relationship between obesity and osteoarthritis. Results: Osteoarthritis burden rose from 1990 to 2021, affecting younger populations, though there was a decline in regions with a high Socio-demographic Index (SDI) between 2001 and 2005. Women experienced a greater burden than men. The increase in disease burden was driven by population growth and rising disease prevalence. There is considerable potential for enhancing osteoarthritis control in most countries. Forward Mendelian randomization analyses demonstrated a significant causal relationship between obesity and osteoarthritis, whereas inverse Mendelian randomization analyses found no evidence of causality from osteoarthritis to obesity at any obesity level. Conclusion: The global rise in disability-adjusted life-years (DALYs) due to BMI-related osteoarthritis mainly due to population growth, affecting women more than men. This study may be a reference point for early and precise intervention in BMI-related osteoarthritis.

Objective: The N7-methylguanosine (m7G) modification is known as a common post-transcriptional modification of RNA that has been found to be involved in the pathogenesis of various diseases. However, its role in osteoarthritis (OA) remains largely unknown. This study aimed to identify the genes associated with m7G modification in OA and further investigate their diagnostic value and immune infiltrates. Methods: We constructed an OA risk model based on key m6A regulators using LASSO regression. Unsupervised clustering analysis was used to detect diverse m7G modification phenotypes and m7G gene clusters based on key m7G regulators in the 106 OA samples. We evaluated the features of the immune microenvironment between distinct risk groups, m7G modification phenotypes, and m7G gene clusters, using immune infiltration analysis. Single-cell analysis was performed to determine the relationship between the key m7G regulators and cartilage degeneration. Finally, in vitro and in vivo experiments were conducted to explore the potential roles of key m7G regulators in OA. Results: Four key m7G regulators, including EIF1, JUND, NUDT16L1 , and NCBP1 , and two risk groups, m7G modification phenotypes, and m7G gene clusters were identified. A nomogram model constructed based on the key m7G regulators demonstrated its predictive role in the occurrence of OA. Moreover, the risk score of the patients in the high-risk group was higher than that of the patients in the low-risk group. Different immune infiltration characteristics were found among the risk groups, m7G modification phenotypes, and m7G gene clusters. Additionally, single-cell analysis confirmed ubiquitous expression of EIF1 and JUND across all chondrocyte subtypes. Furthermore, both genes were downregulated in OA cartilage, and ROC analysis demonstrated that EIF1 and JUND exhibited excellent performance in OA diagnosis. Finally, it was confirmed that inhibiting the expression of EIF1 and JUND induced upregulation of MMP13 and downregulation of collagen II. Further in vivo experiments indicated that suppression of EIF1 and JUND contributed to the progression of OA. Conclusion: Our study revealed four m7G regulators, including EIF1, JUND, NUDT16L1 , and NCBP1 , as novel biomarkers that may be associated with the immune infiltration during the progression of OA. Moreover, EIF1 and JUND may serve as potential therapeutic targets for preventing cartilage degeneration. However, further experiments are required to elucidate the molecular mechanisms underlying OA.