Compound Zhenzhu Tiaozhi Capsule Regulates MEKK2-Wnt Coupling and Antagonizes β-catenin Ubiquitination Improves Glucocorticoid Osteoporosis in Rats

  Objective: To investigate the regulation of mitogen-activated protein kinase 2-Wnt through the intervention of Zhenzhu Tiaozhi capsule (FTZ), a compound that antagonizes β-catenin ubiquitination, bone and cell changes.

  Method: Male SPF rats were randomly divided into normal control group, methylprednisolone group (model group), methylprednisolone + saline group (blank control group) and methylprednisolone + FTZ Group (experimental group). MicroCT examination and histopathological staining of the cancellous bone of the proximal femur were performed to determine the expression of Wnt3a, MEKK2 and β-catenin protein. The BMSC model was extracted and stained with FTZ-containing serum, alkaline phosphatase and alizarin red; measurement of bone formation and differentiation related genes ALP, Runx2, OCN expression; measurement of MEKK2, β-catenin protein expression; and β-catenin/TCF metastasis level .

  Result: 1) Micro-CT compares the experimental group with the model group. The former are BV/TV and Tb. Th, Tb/N, etc. decreased, while Tb/sp increased (P\u003c0.05). OI three-dimensional reconstruction showed that the quality of trabecular bone in the experimental group was improved and partially repaired; 2) In hematoxylin-eosin staining, the trabecular density of the experimental group was higher than that of the model group. The bone trabecular shape is better; compared with the model group, the expression of Wnt3a, MEKK2 and β-catenin in the bone tissue of the experimental group increased (P\u003c0.05); 4) BMSC FTZ-containing serum extracted from the GIOP rat model ( Experimental group) intervention, the results of alkaline phosphatase and Alizarin Red staining showed that experimental bone response was enhanced (P\u003c0.05); 5) Serum intervention containing FTZ made BMSC β-increased the transcriptional activity of catenin/TCF ( P\u003c0.05); promote the expression of β-catenin and MEKK2 protein (P\u003c0.05).

  Conclusion: FTZ can prevent and treat GIOP by regulating MEKK2-Wnt coupling and antagonizing β-catenin ubiquitination, thereby improving the fine structure of bones.