Huogu I formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARγ expression and activating Wnt/LRP5/β-catenin signaling

Jiang, Yini; Liu, Daobing; Kong, Xiangying; Xu, Ying; Chen, Weiheng; Lin, Na

doi:10.1016/s0254-6272(14)60100-x

Cited by 17 publications

(14 citation statements)

References 21 publications

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“…The main TCM function of HGF is to help invigorate the spleen (Pi) to clear dampness, resolve phlegm and activate blood circulation. Previous animal testing had found an allopathic effect of HGF on preventing steroid-treated animals from developing steroid-associated ONFH [17,18]. Interestingly, we found that HGF also helps improve lipoprotein metabolism [17,18].…”

Section: Introductionsupporting

confidence: 51%

“…Previous animal testing had found an allopathic effect of HGF on preventing steroid-treated animals from developing steroid-associated ONFH [17,18]. Interestingly, we found that HGF also helps improve lipoprotein metabolism [17,18]. Further experiments found that the ethyl acetate fraction of HGF helps inhibit the adipogenic differentiation of the bone marrow stromal cells [19] whereas the aqueous fraction of HGF promotes the osteogenic differentiation [20].…”

Section: Introductionmentioning

confidence: 51%

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Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients

Huang

et al. 2020

Journal of Orthopaedic Translation

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A R T I C L E I N F O Keywords: Chinese herbal medicine Huo-Gu formula Osteonecrosis of the femoral head SARS Steroid-related osteonecrosis S U M M A R Y Purpose: The coronavirus disease 2019 (COVID-19) reminds us of the severe acute respiratory syndrome (SARS) outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19.Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by traditional Chinese medicine, and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu formula (HGF) therapy in these patients. Participants and methods: A total of 33 convalescent SARS patients (9 males and 24 females) with bilateral steroidassociated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for 6 months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of 1 year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography and magnetic resonance imaging, were performed to evaluate the outcomes. Results: Based on average 14 years of follow-up of HGF therapy (ranging from 6 to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 precollapse hips (Association Research Circulation Osseous [ARCO] Stage I or II) progressed to femoral head collapse (ARCO Stage III or IV). Only five patients (also 5 hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan-Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. Conclusion: Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases.

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Section: Introductionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 51%

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients

Huang

et al. 2020

Journal of Orthopaedic Translation

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“…PPARγ is an adipogenic transcription factor that is expressed in the very early stage of adipogenesis35. This factor strongly promotes adipogenic differentiation and inhibits osteogenic differentiation36. Research has shown that steroids significantly up-regulate PPARγ expression in rodent and human BMSCs, leading to the time- and dose-dependent induction of adipogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Zhang

et al. 2016

Sci Rep

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The imbalance between adipogenic and osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) plays a significant role in the pathogenesis of steroid-induced osteonecrosis of the femoral head (ONFH). Several microRNAs (miRNAs) are involved in regulating adipogenesis and osteogenesis. In this study, we established a steroid-induced ONFH rat model to identify the potential relevant miRNAs. We identified 9 up-regulated and 28 down-regulated miRNAs in the ONFH rat model. Of these, miR-27a was down-regulated and negatively correlated with peroxisome proliferator-activated receptor gamma (PPARγ) and gremlin 1 (GREM1) expression. Further studies confirmed that PPARγ and GREM1 were direct targets of miRNA-27a. Additionally, adipogenic differentiation was enhanced by miR-27a down-regulation, whereas miRNA-27a up-regulation attenuated adipogenesis and promoted osteogenesis in steroid-induced rat BMSCs. Moreover, miRNA-27a up-regulation had a stronger effect on adipogenic and osteogenic differentiation in steroid-induced rat BMSCs than si-PPARγ and si-GREM1. In conclusion, we identified 37 differentially expressed miRNAs in the steroid-induced ONFH model, of which miR-27a was down-regulated. Our results showed that miR-27a up-regulation could inhibit adipogenesis and promote osteogenesis by directly targeting PPARγ and GREM1. Thus, miR-27a is likely a key regulator of adipogenesis in steroid-induced BMSCs and a potential therapeutic target for ONFH treatment.

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“…Patient‐specific finite element models (FEM) of these participants were generated based on these CT images. All patients received non‐surgical management, including traditional Chinese medicine (TCM) herbal medication (Jianpihuogu Formula) for 180 days and restricted weight bearing with two crutches for 1 year. Table shows baseline data for the 40 participants.…”

Section: Methodsmentioning

confidence: 99%

Prediction of Collapse Using Patient‐Specific Finite Element Analysis of Osteonecrosis of the Femoral Head

Huang

et al. 2019

Orthopaedic Surgery

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Objective To develop a prediction method for femoral head collapse by using patient‐specific finite element analysis of osteonecrosis of the femoral head (ONFH). Methods The retrospective study recruited 40 patients with ARCO stage‐II ONFH (40 pre‐collapse hips). Patients were divided into two groups according to the 1‐year follow‐up outcomes: patient group without femoral head collapse (noncollapse group, n = 20) and patient group with collapse (collapse group, n = 20). CT scans of the hip were performed for all patients once they joined the study. Patient‐specific finite element models were generated based on these original CT images following the same procedures: segmenting the necrotic lesion and viable proximal femur, meshing the computational models, assigning different material properties according to the Hounsfield unit distribution, simulating the stress loading of the slow walking gait, and measuring the distribution of the von Mises stress. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the maximum level of the von Mises stress. The optimal cut‐off value was selected based on the Youden index and the corresponding predictive accuracy was reported as well. Results The mean level of the maximum von Mises stress in the collapse group was 2.955 ± 0.539 MPa, whereas the mean stress level in the noncollapse group was 1.923 ± 0.793 MPa (P < 0.01). ROC analysis of the maximum von Mises stress found that the area under the ROC curve was 0.842 (95% CI: 0.717–0.968, P < 0.01). The maximum Youden index was 0.60, which corresponded to two optimal cut‐off values: 2.7801 MPa (sensitivity: 0.70; specificity: 0.90; predictive accuracy: 80.00%; LR+: 7), and 2.7027 MPa (sensitivity: 0.75; specificity: 0.85; predictive accuracy: 77.50%; LR+: 5). Conclusion Finite element analysis is a potential method for femoral head collapse prediction among pre‐collapse ONFH patients. The maximum level of the von Mises stress on the weight‐bearing surface of the femoral head could be a good biomechanical marker to classify the collapse risk. The collapse prediction method based on patient‐specific finite element analysis is, thus, suitable to apply to clinical practice, but further testing on a larger dataset is desirable.

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Huogu I formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARγ expression and activating Wnt/LRP5/β-catenin signaling

Abstract: The results of our present study highlight the lipid-lowering potential of Huogu I formula, and provide further evidence of the involvement of the PPARgamma inhibition and Wnt/LRP5/ beta-catenin signaling activation in the effects of Huogu I formula.

Cited by 17 publications

References 21 publications

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients

miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Prediction of Collapse Using Patient‐Specific Finite Element Analysis of Osteonecrosis of the Femoral Head

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