Senescent nucleus pulposus mesenchymal stem cells (NPMSCs) are key instigators of local chronic inflammation and disruptions in nucleus pulposus tissue repair in intervertebral disc degeneration (IVDD). This study aimed to investigate the interplay between EZH2 and NPMSCs senescence-associated inflammation. Nucleus pulposus samples were collected from IVDD patients (n = 15, F/M = 7/8, average age 47.9 (21-72) year-old). Multiplex immunohistochemistry was conducted to detect the expression of EZH2 and the cGAS/STING pathway. Subsequently, NPMSCs were isolated from 7 patients (n = 7, F/M = 4/3, average age 49.4 (36-68) year-old). After treatment with tert-butyl hydroperoxide and lentivirus-overexpression-EZH2 (Lv-OE-EZH2), real time fluorescent quantitative PCR, immunofluorescence, western blot, and ChIP were used to detect the expression of EZH2 and the cGAS/STING pathway. Micro-CT, magnetic resonance imaging, and histological staining were performed to assess the therapeutic effects of Lv-OE-EZH2 and a STING inhibitor on rat IVDD. All experiment designs were independent. In both human nucleus pulposus tissues and an in vitro cell model, EZH2 expression decreased while the cGAS/STING pathway became activated in senescent NPMSCs. ChIP assays and Lv-OE-EZH2 experiments validated that EZH2 epigenetically inhibited STING expression via H3K27me3, thereby impairing the cGAS/STING pathway and attenuating senescence-associated inflammation. Moreover, overexpression of EZH2 (Pfirrmann grade means difference -1.375, p = 0.0089) and inhibition of STING effectively attenuated rat IVDD. The decreased expression of EZH2 in senescent NPMSCs promotes senescence-associated inflammation and the progression of IVDD, possibly by relieving the transcriptional inhibition of STING and enabling the activation of the cGAS/STING pathway.

Reports indicate that height significantly impacts bone health, which is a crucial factor in bone mineral density (BMD). The focus of this research was to

Wang Y, et al. Clin Orthop Surg. 2025 Oct;17(5):815-825. https://doi.org/10.4055/cios25087

The albumin-globulin ratio (AGR), which integrates nutritional and inflammatory biomarkers, may reflect skeletal health status; however, its relationship with bone mineral density (BMD) remains inadequately characterized. This cross-sectional analysis utilized data from 10,101 US adults in the National Health and Nutrition Examination Survey 2005 to 2018. Weighted multivariable linear regression was used to evaluate the AGR-BMD associations at the femoral neck and lumbar spine (L1–L4). Generalized additive models identified nonlinearity, with threshold effects quantified by piecewise regression. Subgroup analyses were used to test interactions by sex, race, and comorbidities. After full adjustment, each unit increase in AGR correlated with reduced femoral neck BMD (β = −0.0354 g/cm ² , 95% confidence interval: −0.0464 to −0.0243) and lumbar BMD (β = −0.0245 g/cm ² , 95% confidence interval: −0.0369 to −0.0120). Nonlinear analyses revealed inflection points at AGR = 1.7407 (femoral) and 1.1714 (lumbar), with differential associations below or above thresholds. Women exhibited a 3.1-fold stronger inverse association than men ( P _interaction < .0001). Elevated AGR was independently associated with reduced BMD in adults in the United States, demonstrating nonlinear threshold patterns (1.74 for femoral and 1.17 for lumbar BMD) and pronounced sexual dimorphism. These findings suggest that AGR is a composite biomarker that reflects inflammatory-nutritional pathways that are relevant to skeletal homeostasis.

Diabetes mellitus substantially increases the risk of osteoporosis and fractures, but the mechanisms remain unclear. Dyslipidemia, particularly the role of high-density lipoprotein (HDL), may influence bone mineral density (BMD), yet evidence in diabetic patients is limited. This study aimed to explore the association between HDL and BMD in US adults with diabetes using a nationally representative dataset. We analyzed data from 5 National Health and Nutrition Examination Survey cycles (2005–2018). A total of 5014 diabetic participants with available HDL and dual-energy X-ray absorptiometry (DXA)-measured BMD were included. Weighted multivariable linear regression models, smooth curve fitting, and 2-piecewise linear regression were employed to examine linear and nonlinear associations. Subgroup and sensitivity analyses were also conducted to assess robustness. Among 5014 participants (mean age 40.1 ± 31.2 years; 50.8% male), mean femoral neck and lumbar spine BMD were 0.81 and 1.03 g/cm ² , respectively, with a mean HDL of 48.9 mg/dL. Higher HDL levels were inversely associated with BMD at both the femoral neck (β = −0.0011, 95% CI: −0.0015 to −0.0007) and lumbar spine (β = −0.0012, 95% CI: −0.0018 to −0.0007) after full adjustment. Participants in the highest HDL quartile had significantly lower BMD compared with those in the lowest quartile (femoral neck: −0.0294 g/cm ² ; lumbar spine: −0.0378 g/cm ² ). Smooth curve fitting indicated nonlinear, negative associations. Subgroup analyses revealed stronger inverse associations in men, participants with hypertension, those <60 years at the femoral neck, and those ≥60 years at the lumbar spine. Sensitivity analyses confirmed the robustness of the results. Higher HDL levels were consistently and independently associated with lower BMD in US adults with diabetes. These findings challenge the traditional view of HDL as universally protective, suggesting that in the diabetic context, elevated HDL may exert detrimental effects on bone health. Further longitudinal and mechanistic studies are warranted to clarify causal pathways and guide osteoporosis prevention strategies in this high-risk population.