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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.
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Objective To establish the GIOP model and extract BMSCs from the rat model.We aim to in-vesitigatethe effect ofrhPTH(1-34)for inhibiting β-catenin ubiquitination when combining with Micro-CT and bio-logical technology.We also investigate the influence of rhPTH(1-34)on the GIOP.Methods Female SPF emale rats wererandomly divided into normal control group,methylprednisolone group(model group),methylpredniso-lone+saline group(blankcontrol group)and methylprednisolone+rhPTH(1-34)group(test group). The proximal femoral cancellous bone was examined by Micro-CTand histopathological Staining. The expression of Wnt10b and β-catenin protein were detected. By comparing with inducedBMP-2,BMSCs were treated withrhPTH(1-34)and stained with ALP and alizarin red.Results(1)In Micro-CT,BV/TV,Tb.Th and Tb/N decreased,whereas Tb/sp increased in the test group comparedwith model group(P<0.05).ROI three-dimensional reconstruction of trabecu-lar bone in test group showed local bone repair;(2)Wnt10b and β-cateninexpression increased in the test group compared with the model model(P<0.05),indicating that rhPTH(1-34)can enhance the transcriptional activity of β-catenin(P<0.05)and promote the expression of Wnt10b andβ-catenin(P<0.05).Conclusion The inter-vention with rhPTH(1-34)can prevent GIOP by regulating the Wnt/β-catenin signaling pathway and inhibiting GIOP progress,which can improve the microstructure of bone.
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Objective To investigate the long and mid-term clinical outcomes of the impacting bone graft and impact factors in treating osteonecrosis of femoral head (ONFH).Methods Impacting bone graft was utilized to treat 54 patients (64 hips)with ONFH.There were 44 cases male and 10 female with an average age of 35.44±8.86 (range,20-55) years.There were 5 hips caused by trauma,23 hips by glucocorticoid administration,28 hips by intake of alcohol,4 hips by alcohol and glucocorticoid induced,and 4 hips by idiopathic factors.There were 14 hips at ARCO (Association Research Circulation Osseous) stage Ⅱ,50 hips at stage Ⅲ and 6 hips at JIC (Japanese Osteonecrosis Investigation Committee) type B,23 hips at type C1,35 hips at C2 type.Harris hip score (HHS) was used to evaluate the clinical effects.Potential factors,including age,etiologies,pain duration,ARCO stage and JIC type,were evaluated to investigate their impacts on clinical outcomes.Surgery failure was defined as diverting to other surgeries,or poor HHS score evaluation (＜70 points).The survival time of femoral head was defined as the interval between time of impacting bone graft and the failure of surgery.Results The mean follow-up duration was 8.61 ± 1.45 (range,5.13-10.84) years.The proportion of patients with excellent or good Harris score was 81.3％ (52/64).The excellent or good rate was 76.0％ (38/50) at 8 years follow-up.Furthermore,the total survival rate of femoral head was 92％ at 8 years follow-up.The number of surgical failure was 10 (12 hips) and the failure rate was 18.8％ (12/64).There were no significant differences in ages,etiologies,pain duration,ARCO stage and JIC type among these patients before surgery (P ＜ 0.05).There were significant differences in the post-operational Harris score and excellent or good rate among the 20-30 years group,31-40 years group and over 40 years group (P ＜ 0.05).No significant difference for both two indexes was observed among different etiologies (P ＞ 0.05).When considering the duration after the initial pain,there were significant differences among 6 months group,7-12 months group and over 12 months group (P ＜0.05).There were significant differences between the Ⅲa stage and Ⅲc stage (P＜ 0.05),and between the C1 type and C2 type (P ＜ 0.05).Multifactor Logistic regression showed that there was closely relationship between the Harris score (excellent or good rate) after surgery and pain duration,ARCO stage,JIC type (P ＜ 0.05).Conclusion Impacting bone graft for ONFH is satisfy in the long and mid-term follow up duration.Impacting bone graft would be more suitable for patients with the collapse less than 2 mm,the lateral wall preservation and interval after the initial pain less than 12 months.
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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.
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BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head remains unclear. Femoral head reconstruction after colapse is related to the bone remodeling due to disorder of the bone formation-absorption coupling. “Removing Blood Stasis” Method has been shown to have a positive effect on the disease in clinics. However, the mechanisms by which the “Removing Blood Stasis” Method confers bone repair after osteonecrosis remain poorly understood. OBJECTIVE:To explore the effect of “Removing Blood Stasis” Method on bone repair in rabbits with steroid-induced femoral head osteonecrosis. METHODS: Fifty New Zealand rabbits were randomly assigned into three groups: normal control (n=10), model (n=20) andTaohong Siwu Decoction (n=20) groups, respectively. The steroid-induced osteonecrosis of the femoral head animal models were established by intramuscular injection of endotoxin combined with methylprednisolone (MPS). Rabbits inTaohong Siwu Decoction group were intragastricaly administered with 0.3 g/kg ofTaohong Siwu Decoction suspension after the last injection of methylprednisolone. The control and model groups were administrated by equal volume of ultrapure water for 8 consecutive weeks. High-resolution MRI and pathological determinations were used to assess the successful models. Protein expression levels of ABCB1, RUNX2, OPN, RANK, RANKL, PPAR, osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) in rabbit femoral heads were detected by western blot assay. RESULTS AND CONCLUSION:(1) Hematoxylin-eosin staining showed that trabecular bone fracture, karyopyknosis, empty lacunae, necrotic bone marrow cels were seen in the model group. Empty lacunae rate in the model group was significantly different from that in the normal control group (P < 0.05). Bone formation was active and kept better trabecular morphology in theTaohong Siwu Decoction group. It suggested that “Removing Blood Stasis” Method can improve repair of necrotic area. (2) In the model group, femoral head with a wide range of low-density areas in high-resolution MRI;Taohong Siwu Decoction group showed the relatively normal shape of the femoral head with smal areas of low density. It suggested that “Removing Blood Stasis” Method can improve image changes in the necrotic area. (3) Protein expression levels of RUNX2, RANK, RANKL were significantly up-regulated but protein expression levels of ABCB1, OPG, VEGF were significantly down-regulated in the model group compared with the normal control group; whereas, they were al significantly up-regulated in theTaohong Siwu Decoction group compared with the model group, except for RANK and RANKL (P < 0.05). These results suggest that the “Removing Blood Stasis” Method can promote bone repair in steroid-induced femoral head osteonecrosis rabbits by regulating protein expressions of ABCB1, RUNX2, RANK, RANKL, OPG, and VEGF.
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BACKGROUND: A variety of angiogenic factors are involved in bone healing after osteonecrosis of the femoral head. OBJECTIVE:To explore the role and mechanism of angiogenic factors in osteonecrosis of the femoral head. METHODS: A computed-based online search of PubMed, Google and SpringerLink databases was performed using the key words of “angiogenic factors, osteonecrosis of the femoral head, vascular endothelial growth factor, angiopoietin-1, fibroblast growth factor-2, hypoxia inducible factor-1, calcitonin gene related peptide and hypoxia inducible factor-1α” for literatures published from December 1980 to May 2015. RESULTS AND CONCLUSION:Finaly, 68 articles were included. Bone angiogenesis which is dependent on special signaling factors in the microenvironment is closely linked with bone repair. A variety of cytokines, such as vascular endothelial growth factor, angiopoietin-1, fibroblast growth factor-2, platelet-derived growth factor, calcitonin gene-related peptide, and hypoxia inducible factor-1α, have been identifiedto control angiogenesis in different ways and be involved in the repair of necrotic femoral head.