Aqueous Fraction of Huogu Formula Promotes Osteogenic Differentiation of Bone Marrow Stromal Cells Through the BMP and Wnt Signaling Pathways

Kong, Xiangying; Li, Xiaomin; Zhang, Cun; Zhu, Linyu; Wan, Heng; Zhu, Jiang; Liu, Cuiling; Su, Hongchang; Qin, Qingxia; Chen, Weiheng; Lin, Na

doi:10.1089/rej.2015.1795

Cited by 5 publications

(6 citation statements)

References 48 publications

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“…Functionally, activated Wnt and BMP signaling pathways were reported to increase the ALP activity and promote the osteoblast differentiation . Similarly, the BMP and Wnt signaling pathways co‐operatively involve in the function of an aqueous fraction of Huogu, which increased ALP activity, mineralized nodules, and migration of MSCs, and further enhance osteogenesis with elevated expression of Runx2, ALP, OCN, and osterix . Together, we maintained that the activation of Wnt and BMP signaling pathways could result in the upregulation of EMX2, which promoted differentiation of MSCs into osteoblasts in MM patients.…”

Section: Discussionsupporting

confidence: 57%

“…A previous study has revealed that Wnt/β-catenin signaling pathway could increase BMP2 expression in osteoblasts. 40 Together, we maintained that the activation of Wnt and BMP signaling pathways could result in the upregulation of EMX2, which promoted differentiation of MSCs into osteoblasts in MM patients. F I G U R E 5 Activated Wnt signaling increased the BMP9 protein expression.…”

Section: Discussionmentioning

confidence: 55%

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Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

Wei

Chen

et al. 2018

J of Cellular Biochemistry

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Osteoblast differentiation, defined as the process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, is directly linked to multiple myeloma (MM) bone disease. Wnt and bone morphogenetic protein (BMP) are proved to be implicated in the pathological or defective osteoblast differentiation process. This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray‐based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co‐operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The expression patterns of Wnt and BMP pathway–related genes, EMX2 and osteoblast differentiation‐related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co‐operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced differentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co‐operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 55%

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

Wei

Chen

et al. 2018

J of Cellular Biochemistry

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“…In mainland China, orthopaedic surgeons can also choose Chinese medicine as a treatment method for patients 17, 18 . Considerable experimental work has been done in this area 19–22 , and a large number of patients who received hip‐sparing therapy with integrated medicine achieved satisfactory results 23 . However, the epidemiology of ONFH has not been as thoroughly investigated as its treatment; studying its epidemiology is particulary important for a country like China with a large land area and population.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological Study Based on China Osteonecrosis of the Femoral Head Database

Tan

Zeng

et al. 2020

Orthopaedic Surgery

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Objective The aim of the present study was to reveal the case characteristics of osteonecrosis of the femoral head (ONFH) in Mainland China. Methods This cross‐sectional epidemiological study derived data for ONFH patients from July 2016 to December 2018 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The derived data included gender, age, body mass index (BMI), height, occupation, region, and etiology of femoral head necrosis. A descriptive analysis was performed to summarize the epidemiological characteristics of the case data in the CONFHD. Results A total of 1844 ONFH patients (2945 hips) were included in this study, comprising 1302 men and 542 women. The age of patients ranged from 18 to 95 years, with a median of 50 years, and the male to female ratio was 2.4. Male patients are younger than female patients (48.26 ± 12.56 years old and 55.56 ± 14.94 years old, respectively). Among the 1844 patients (2945 hips), there were 528 (17.92%) hips at ARCO stage I, 941 (31.99%) hips at ARCO stage II, 873 (29.63%) hips at ARCO stage III, and 603 (20.46%) hips at ARCO stage IV. In the subclassification of ARCO stages I and II, the majority of cases were type C; type A comprised the majority in the subclassification of ARCO stage III. According to the Kellgren–Lawrence classification system, among the 603 ARCO stage IV hips, there were 178 (29.52%) grade 1 hips, 201 (33.34%) grade 2 hips, 176 (29.18%) grade 3 hips, and 48 (7.96%) grade 4 hips. Most were from three provinces: Henan (27.3%), Shanxi (13.9%), and Shandong (11.9%). Regarding BMI, 982 patients (53.25%) were overweight or obese. Among all patients, the largest proportion of patients engaged in level IV manual work. Of all the patients, there were 495 (26.84%) with steroid‐induced ONFH, 685 (37.15%) were alcoholics, and 290 (15.73%) had traumatic ONFH. The 495 patients with steroid‐induced ONFH included 278 men (56.16%) and 217 women (43.84 %), had a complete history of hormone use. Among the primary diseases, there were 195 cases (39.39%) of immune system diseases, followed by dermatological diseases, respiratory diseases, nephropathy, and other diseases. There were a total of 685 patients with alcoholic ONFH, 589 of these patients (85.99%) were men. A total of 188 (27.45%) patients had drunk alcohol for 6–10 years (comprising the highest proportion), and 280 patients (40.88%) consumed 3001–3500 mL of alcohol each week (the highest proportion). Conclusion Osteonecrosis of the femoral head most commonly occurs after the age of 40. Male patients have an earlier onset than female patients, and the number of male patients is approximately twice that of female patients. The BMI of patients was mainly in the overweight and obese range, and half of these patients engaged in level IV manual work. From the imaging findings, the numbers of hips at ARCO stages II and III were greatest, and the number at stage I was relatively small. Among all the causes of disease, alcohol, steroid use and trauma were the three most common reasons for ONFH.

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“…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]. Here, we conducted a long-term retrospective study to evaluate the outcomes of HGF therapy for steroid-associated ONFH in convalescent SARS patients with an average of 14 years.…”

Section: Introductionmentioning

confidence: 98%

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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Aqueous Fraction of Huogu Formula Promotes Osteogenic Differentiation of Bone Marrow Stromal Cells Through the BMP and Wnt Signaling Pathways

Cited by 5 publications

References 48 publications

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

Epidemiological Study Based on China Osteonecrosis of the Femoral Head Database

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

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