Menopause modified the association of blood pressure with osteoporosis among gender: a large-scale cross-sectional study.

Purpose: This study aimed to assess the potential association between blood pressure and osteoporosis in a rural population with limited resources. Existing evidence on this association is limited, particularly in such settings. Methods: Data from 7,689 participants in the Henan Rural Cohort study were analyzed. Four blood pressure indicators [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP)] were measured. The logistic regression model and restricted cubic spline plots were used to assess the relationship between blood pressure indicators and osteoporosis prevalence. Results: Positive trends were noted between blood pressure indicators and osteoporosis prevalence in the entire group and women (P trend < 0.05 for SBP, MAP, and PP). Women with higher SBP and PP exhibited elevated odds of osteoporosis compared with those with the lowest SBP and PP (ORs ranging from 1.15 to 1.5 for SBP and 1.06 to 1.83 for PP). No such associations were found in men. These relationships were only evident in postmenopausal women. Dose-response analysis confirmed these findings. Excluding participants taking hypertension medication did not alter the results. Conclusion: In resource-limited settings, higher SBP and PP are associated with the increased prevalence of osteoporosis in women, potentially influenced by menopause-related factors. This indicates that potential gender-based differences and social inequalities may affect bone health. Clinical trial registration: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) http://www.chictr.org.cn/showproj.aspx?proj=11375.

Formononetin inhibits IL-1ß-induced inflammation in human chondrocytes and slows the progression of osteoarthritis in rat model via the regulation of PTEN/AKT/NF-κB pathway.

BACKGROUND/AIM: Osteoarthritis (OA) is a common degenerative disease characterized by cartilage degradation and inflammation. This study aimed to investigate the anti-inflammatory properties of formononetin, an isoflavone extracted from astragalus membranaceus, on OA. METHODS: Human OA chondrocytes were pretreated in vitro with formononetin and subsequently stimulated with IL-1ß. The production of inflammatory mediators, cytokines and the synthesis of catabolic factors were evaluated by ELISA and Western blot analysis. In addition, a rat model of OA was established and treated with formononetin. RESULTS: Formononetin attenuated the overproduction of inflammatory mediators and cytokines, suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and inhibited the synthesis of catabolic factors such as MMPs and thrombospondin motifs 5. Furthermore, formononetin exerted protective effects in a rat model of OA. Mechanistically, we found that formononetin inhibited IL-1ß induced activation of nuclear factor kappa B and AKT by activating the phosphatase and tensin homolog. CONCLUSIONS: Formononetin could be used as a potential agent for OA treatment.

Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway.

Osteoarthritis (OA) is a complex condition that involves both apoptosis and senescence and currently cannot be cured. Fibroblast growth factor 21 (FGF21), known for its role as a potent regulator of glucose and energy metabolism, protects from various diseases, possibly by mediating autophagy. In the present study, the role of FGF21 in the progression of OA was investigated in both in vitro and in vivo experiments. In vitro, the results revealed that FGF21 administration alleviated apoptosis, senescence, and extracellular matrix (ECM) catabolism of the chondrocytes induced by tert-butyl hydroperoxide (TBHP) by mediating autophagy flux. Furthermore, CQ, an autophagy flux inhibitor, could reverse the protective effect of FGF21. It was observed that the FGF21-induced autophagy flux enhancement was mediated by the nuclear translocation of TFEB, which occurs due to the activation of the SIRT1-mTOR signaling pathway. The in vivo experiments demonstrated that FGF21 treatment could reduce OA in the DMM model. Taken together, these findings suggest that FGF21 protects chondrocytes from apoptosis, senescence, and ECM catabolism via autophagy flux upregulation and also reduces OA development in vivo, demonstrating its potential as a therapeutic agent in OA.

Maltol prevents the progression of osteoarthritis by targeting PI3K/Akt/NF-κB pathway: In vitro and in vivo studies.

Osteoarthritis (OA), a prevalent degenerative arthritis disease, principle characterized by the destruction of cartilage and associated with the inflammatory response. Maltol, a product formed during the processing of red ginseng (Panax ginseng, CA Meyer), has been reported to have the potential effect of anti-inflammatory. However, its specific mechanisms are not demonstrated. We investigated the protective effect of maltol in the progression of OA both in vitro and in vivo experiments. Human chondrocytes were pre-treated with maltol (0, 20, 40, 60 µM, 24 hours) and incubated with IL-1ß (10 ng/mL, 24 hours) in vitro. Expression of PGE2, TNF-α and NO was measured by the ELISA and Griess reaction. The expression of iNOs, COX-2, aggrecan, ADAMTS-5, MMP-13, IκB-α, p65, P-AKT, AKT, PI3K and P-PI3K was analysed by Western blotting. The expression of collagen II and p65-active protein was detected by immunofluorescence. Moreover, the serious level of OA was evaluated by histological analysis in vivo. We identified that maltol could suppress the IL-1ß-stimulated generation of PGE2 and NO. Besides, maltol not only suppressed the production of COX-2, iNOs, TNF-α, IL-6, ADAMTS-5, MMP-13, but also attenuated the degradation of collagen II and aggrecan. Furthermore, maltol remarkably suppressed the phosphorylation of PI3K/AKT and NF-κB induced by IL-1ß in human OA chondrocytes. Moreover, maltol could block the cartilage destroy in OA mice in vivo. To date, all data indicate maltol is a potential therapeutic agent by inhibiting inflammatory response via the regulation of NF-κB signalling for OA.

The protective effect of Ellagic acid (EA) in osteoarthritis: An in vitro and in vivo study.

Osteoarthritis (OA), a progressive joint disorder, is principally characterized by the degeneration and destruction of the articular cartilage. Ellagic acid (EA), a natural polyphenol found in berries and nuts has shown potent anti-inflammatory effects, however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we reported the anti-inflammatory effects of Ellagic acid (EA) in the progression of OA in both in vitro and in vivo experiments. in vitro study, IL-1ß-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) were inhibited by Ellagic acid (EA). Moreover, Ellagic acid (EA) down-regulated the IL-1ß-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) while up-regulated the collagen of type II and aggrecan. Mechanistically, we revealed that Ellagic acid (EA) suppressed nuclear factor kappa B (NF-κB) signaling in IL-1ß -induced chondrocytes. And Ellagic acid (EA)-induced protectiveness in OA development was also shown by the DMM model. Taken together, our data indicate that Ellagic acid (EA) may serve as a potential drug for OA treatment.

Resveratrol inhibits phosphorylation within the signal transduction and activator of transcription 3 signaling pathway by activating sirtuin 1 in SW1353 chondrosarcoma cells.

The present study assessed the mechanism by which resveratrol (Res) inhibits the growth of SW1353 chondrosarcoma cells and examined whether sirtuin 1 (Sirt1) activation affects phosphorylation within the signal transduction and activator of transcription 3 (STAT3) signaling pathway. The present study used SW1353 chondrosarcoma cells in the logarithmic phase of growth (control and treatment groups). The latter group was treated with Res at 25 and 50 µmol/l for 24 h, and cell viability, proliferation and apoptosis were analyzed using the cell counting kit­8 assay, colony counting and Hoechst staining, respectively. The expression levels of caspase­3, cleaved caspase­3, B­cell lymphoma­2 (BCL­2), BCL-2 associated X protein (Bax), STAT3 and phosphorylated (p­)STAT3) were measured by Western blotting. SW1353 cells were transfected with small interfering (si)RNA targeting Sirt1 and the expression levels of Sirt1, STAT3 and p-STAT3 were assessed. Exposure of SW1353 cells to Res reduced cell viability in a dose­dependent manner (P<0.01). Additionally, cell proliferation was significantly inhibited and the cell nuclei exhibited apoptotic characteristics. Cleaved caspase­3, Sirt1 and Bax levels were upregulated. The expression levels of BCL­2 and p­STAT3 were downregulated. Additionally, the BCL­2/Bax ratio was reduced compared with the control group. The total STAT3 level was unaffected. Res treatment activated Sirt1, however, in cells transfected with Sirt1­siRNA, the ability of resveratrol to suppress p­STAT3 expression was compromised. Overall, it was revealed that Res treatment induced apoptosis, inhibited proliferation and affected phosphorylation within the STAT3 signaling pathway by activating Sirt1 in SW1353 chondrosarcoma cells.