ABSTRACT
Objective To establish a rat model of glucocorticoid-induced osteoporosis(GIOP)and to explore the interventional effect of the Chinese medicine Fufang Zhenzhu Tiaozhi(FTZ)capsules on regulation of mitogen-activated protein kinase kinase kinase 2(MEKK2)-Wnt coupling and inhibiting β-catenin ubiquitination, and to investigate the effect of FTZ on the bone mineral density and cell osteogenic ability. Methods SPF male rats were randomly divided into normal control group,methylprednisolone group(model group),methylprednisolone + saline group(blank control group) and methylprednisolone + FTZ group(experimental group). The proximal femoral cancellous bone was examined by mi-cro-CT and histopathology,and assessment of expressions of Wnt3a,MEKK2,and β-catenin proteins. Bone mesenchymal stem cells(BMSCs were isolated and treated with serum containing FTZ,stained by alkaline phosphatase and alizarin red. The expressions of osteogenic differentiation-related genes ALP,Runx2 and OCN,the expressions of MEKK2 and β-catenin proteins,and the transcription level of β-catenin/TCF were determined. Results 1)The micro-CT imaging showed that compared with the control group, the BV/TV, Tb.Th and Tb/N expressions were significntly decreased, and Tb/sp in-creased in the experimental group(P<0.05). Region of interest(ROI)three-dimensional reconstruction of trabecular bone in the experimental group showed improvement of bone trabeculae and local bone repair. 2)The pathology using he-matoxylin and eosin staining showed that in the experimental group,the bone trabecular density was higher than that of the model group,and observed a better trabecula morphology. 3)The Wnt3a,MEKK2 and β-catenin expressions in the exper-imental group were significantly increased compared with the model model(P<0.05). 4)After treated with FTZ and BMP2,the result of alkaline phosphatase and alizarin red staining indicated an enhanced osteogenic response(P<0.05) in the GIOP rat models. 5)After treatment with seum containing FTZ,The BMSCs isolated from the GIOP rats enhanced the transcriptional activity of β-catenin/TCF/LEF(P<0.05)and promoted the expression of β-catenin and MEKK2 pro-teins(P<0.05). Conclusions FTZ can ameliorate GIOP by regulating the MEKK2-Wnt coupling and inhibiting the β-catenin ubiquitination,and improve the bone microstructure.
ABSTRACT
BACKGROUND:At present, finite element analysis technology can set up the model, predict diagnosis, treatment design, as wel as surgical plan, and can be used in the treatment of necrosis of femoral head. OBJECTIVE:To sum and discuss recent progress in clinical and experimental research regarding biomechanical study in osteonecrosis of femoral head by using finite element analysis. METHODS:A computer-based retrieval was performed by the authors (Hong Guo-ju and Zhou Guang-quan) in PubMed, Google, SpringerLink, ChinaNational Knowledge Infrastructure databases for literatures published from January 2010 to December 2015. The key words were“(finite element analysis OR finite element) AND (osteonecrosis OR osteonecrosis of femoral head)”. Inclusive criteria:studies with contents closely related to this paper;original papers with reliable topics and evidence;or papers with clear points and al-round analysis and both studies in vitro and in vivo. RESULTS AND CONCLUSION:A total of 27 studies were included. The articles in the latest five years related to femoral head osteonecrosis and finite element analysis application were concentrated on. We summarized the latest research progress and problems, including the applied research carried out in the femoral head osteonecrosis clinical cases, innovational skil s, so as to point out the direction of future research in the finite element analysis.