Does the Relationship Between Bone Cement and the Intravertebral Cleft of Kummell Disease Affect the Efficacy of PKP?

OBJECTIVE: To study the relationship between distribution of bone cement and intravertebral cleft of patients with Kummell disease on the clinical effect of percutaneous kyphoplasty (PKP). METHODS: According to the relationship between the distribution of bone cement and the cleft in the vertebrae, a total of 92 patients with Kummell disease who underwent PKP in our hospital were divided into 2 groups. Specifically, the bone cement of patients in group A was localized in the cleft of the vertebrae and did not infiltrate around the cleft, while that of group B patients not only filled the cleft of the vertebrae, but also distributed diffusely around the cleft of the vertebrae. The amount of bone cement injected, leakage rate, visual analogue scale (VAS) score, Oswestry Disability Index (ODI), and vertebral imaging changes before operation, and 2 days and 1 year after operation were compared between the 2 groups. RESULTS: The amount of bone cement injected and the permeability of bone cement in group B were higher than those in group A (P < 0.05). The scores of VAS and ODI in both groups were significantly improved after operation, but the two scores in group B were better than those in group A one year after operation. The height of anterior vertebral body and Cobb's angle of kyphosis in the 2 groups were significantly improved after operation, but 1 year after operation, those in group B were better than those in group A. CONCLUSIONS: PKP was an effective method for treating Kummell disease. At the same time, the relationship between the distribution of bone cement and the cleft in the vertebral body was an important factor affecting the curative effect after PKP. The effect of the distribution pattern of bone cement filled with intravertebral cleft and diffusely distributed around the fissures was better than that of bone cement confined in the vertebral cleft.

Uncovering the Key miRNAs and Targets of the Liuwei Dihuang Pill in Diabetic Nephropathy-Related Osteoporosis based on Weighted Gene Co-Expression Network and Network Pharmacology Analysis.

BACKGROUND: Diabetic nephropathy-related osteoporosis (DNOP) is the most common comorbid bone metabolic disorder associated with diabetes mellitus (DM). The Liuwei Dihuang Pill (LWD) is a traditional Chinese herbal medicine widely used to treat diabetic complications, including diabetic nephropathy (DN). This study aimed to identify the biomarkers of the mechanisms of DNOP in LWD with systems biology approaches. METHODS: Herein, we performed an integrated analysis of the GSE51674 and GSE63446 datasets from the GEO database via weighted gene co-expression network and network pharmacology (WGCNA) analysis. In addition, a network pharmacology approach, including bioactive compounds, was used with oral bioavailability (OB) and drug-likeness (DL) evaluation. Next, target prediction, functional enrichment analysis, network analysis, and virtual docking were used to investigate the mechanisms of LWD in DNOP. RESULTS: WGCNA successfully identified 63 DNOP-related miRNAs. Among them, miR-574 was significantly upregulated in DN and OP samples. A total of 117 targets of 22 components associated with LWD in DNOP were obtained. The cellular response to nitrogen compounds, the AGERAGE signaling pathway in diabetic complications, and the MAPK signaling pathway were related to the main targets. Network analysis showed that kaempferol and quercetin were the most significant components. MAPK1 was identified as a potential target of miR-574 and the hub genes in the protein-protein interaction (PPI) network. The docking models demonstrated that kaempferol and quercetin had a strong binding affinity for Asp 167 of MAPK1. CONCLUSION: This study demonstrated that miR-574 may play important roles in DNOP, and the therapeutic effects of kaempferol and quercetin on LWD in DNOP might be mediated by miR-574 by targeting MAPK1. Our results provide new perspectives for further studies on the anti-DNOP mechanism of LWD.

Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/ß-catenin signaling pathway in diabetic nephropathy-related osteoporosis.

The effects of Liuwei Dihuang pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. The present study aimed to evaluate the effects of LWDH on KDM7A and Wnt/ß-catenin signaling pathway in DNOP rats and the high glucose-induced MC3T3-E1 cells. A DNOP model was prepared by streptozotocin in 9-week-old male Sprague-Dawley (SD) rats to evaluate the effects of LWDH. The cell viability and differentiation capacity of high glucose-induced MC3T3-E1 cells were determined by CCK-8 assay, Alizarin Red staining, and alkaline phosphatase (ALP) staining, respectively. Furthermore, the expressions of KDM7A and Wnt1/ß-catenin pathway-related proteins were determined by Western blot analysis. Treatment of DNOP rats with LWDH could significantly ameliorate the general state, degradation of renal function, and renal pathological changes. LWDH decreased the levels of TNF-α, IL-6, IL-8, IL-1ß, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium and phosphorus in the urine. Besides, LWDH significantly improved bone mineral density (BMD), bone volume (BV), and the bone microstructure of DNOP rats. Moreover, LWDH increased the levels of the elastic modulus, ultimate load, and bending strength in the femurs. In MC3T3-E1 cells, serum-containing LWDH significantly increases in cell viability and osteoblastic differentiation capability. The expression of α-SMA, vimentin, KDM7A, Wnt1 and ß-catenin were significantly down-regulated, and the E-cadherin, H3K9-Me2, H3K27-Me2, BMP-4, BMP-7, Runx2, osteocalcin, and Col1a1 were significantly up-regulated with LWDH treatment. The present study shows that LWDH has a therapeutic effect on DNOP, in part, through down-regulation of KDM7A and Wnt/ß-catenin pathway.

Catalpol Promotes the Proliferation and Differentiation of Osteoblasts Induced by High Glucose by Inhibiting KDM7A.

INTRODUCTION: The protective effect of catalpol on diabetic osteoporosis (DOP) and its mechanism remain unclear. This study aimed to explore whether catalpol enhanced the proliferation and differentiation of MC3T3 cells induced by high glucose by inhibiting the expression of KDM7A. METHODS: MC3T3 cells were induced by high glucose (HG) and treated with different concentrations of catalpol. The proliferation and mineralization abilities of MC3T3-E1 cells were determined by CCK-8 assay and Alizarin Red Staining, respectively. The expression of differentiation-related osteogenic proteins, KDM7A and related proteins of Wnt/ß-catenin signaling pathway was analyzed by Western blot analysis. The alkaline phosphatase (ALP) activity was detected by ALP assay kits. RESULTS: MC3T3-E1 cells induced by high glucose showed decreased proliferation and mineralization abilities and decreased ALP activity, which were all reversed by the treatment of catalpol. High glucose induction inhibited the expression of KDM7A, Total-ß-catenin, Nuclear-ß-catenin and p-GSK3ß, which was reversed by the treatment of catalpol. And KDM7A interference up-regulated the expression of Total-ß-catenin, Nuclear-ß-catenin and p-GSK3ß, which was down-regulated by KDM7A overexpression. Furthermore, the proliferation and mineralization abilities and ALP activity were improved when treated with KDM7A interference and decreased when treated with KDM7A overexpression. However, SKL2001 could improve the proliferation and mineralization abilities and ALP activity of MC3T3-E1 cells. DISCUSSION: Catalpol promotes the proliferation and differentiation of osteoblasts induced by high glucose by regulating the Wnt/ß-catenin signaling pathway through KDM7A.