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Journal ArticleDOI: 10.1080/14712598.2021.1862790

Core decompression isolated or combined with bone marrow-derived cell therapies for femoral head osteonecrosis.

04 Mar 2021-Expert Opinion on Biological Therapy (Expert Opin Biol Ther)-Vol. 21, Iss: 3, pp 423-430
Abstract: Objectives: The regenerative capabilities of bone marrow-derived cell therapies (BMCTs) have been employed in combination with core decompression (CD) in the management of osteonecrosis of the femo...

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Open accessJournal ArticleDOI: 10.1186/S13018-021-02389-3
Abstract: Curculigoside is a natural phenolic glycoside compound produced by Curculigo orchioides Gaertn. This study aimed to explore the effects of curculigoside in promoting the osteogenic differentiation of adipose-derived stem cells (ADSCs) as well as the underlying mechanism. ADSCs were treated with curculigoside at different concentrations (0 μmol/L, 1 μmol/L, 2.5 μmol/L, 5 μmol/L, 10 μmol/L, and 20 μmol/L), and cell viability was assessed by CCK-8 assay. Then, the alkaline phosphatase (ALP) activity was determined, and alizarin red S (ARS) staining was performed to measure the extracellular mineralization of curculigoside. Information about protein-chemical interactions is provided by the search tool for interactions of chemicals (STITCH) database. Then, LY294002 was administered to explore the mechanism by which curculigoside promotes the osteogenic differentiation of ADSCs. Western blot assays were performed to assess changes in the expression of osteogenic-related markers and the phosphorylation of PI3K and AKT. Finally, we established an ovariectomized (OVX)-induced osteoporosis mouse model and administered curculigoside to explore the effects of curculigoside in preventing bone loss in vivo. The CCK-8 assay indicated that curculigoside did not induce cytotoxicity at a concentration of 5 μmol/L after 48 h. The ALP and ARS results revealed that the induced group had higher ALP activity and calcium deposition than the control group. Moreover, the curculigoside group exhibited increased biomineralization, ALP activity, and ARS staining compared to the induced and control groups, and these effects were partially inhibited by LY294002. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the target genes of curculigoside were mainly involved in the PI3K-Akt signaling pathway. PCR and western blot analysis showed that the expression of RUNX2, ALP, and Osterix was upregulated in curculigoside-treated ADSCs, but this effect was partially reversed by the PI3K inhibitor LY294002. Moreover, the curculigoside-treated group exhibited significantly increased phosphorylation of AKT to P-AKT compared with the osteogenic induction group. After treatment with curculigoside, the mice had a higher bone volume than the OVX mice, suggesting partial protection from cancellous bone loss. In addition, when LY294002 was added, the protective effects of curculigoside could be neutralized. Curculigoside could induce the osteogenic differentiation of ADSCs and prevent bone loss in an OVX model through the PI3K/Akt signaling pathway.

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Topics: Curculigoside (83%), Curculigo orchioides (52%)

3 Citations


Open accessJournal ArticleDOI: 10.1186/S13018-021-02386-6
Haiping Zhang1, Ziliang Yu1, Farui Sun2, Jin Jin3Institutions (3)
Abstract: The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells. GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression. We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model. In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.

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Topics: PI3K/AKT/mTOR pathway (53%), Akt/PKB signaling pathway (53%), Osteoblast (52%) ... show more

2 Citations


Open accessJournal ArticleDOI: 10.1186/S13018-021-02246-3
Ke Jie, Wenjun Feng1, Feilong Li1, Keliang Wu1  +4 moreInstitutions (1)
Abstract: Osteonecrosis of the femoral head (ONFH) is a disabling disease, which often involves young patients. Recently, various hip-preserving surgeries were recommended to delay total hip arthroplasty (THA). This study aimed to compare clinical outcomes and survival rate in the long-term follow-up between core decompression combined with a non-vascularized autologous fibular graft (group A) and an allogeneic fibular graft (group B) for the treatment of ONFH. We retrospectively evaluated 117 patients (153 hips) with ONFH (Association Research Circulation Osseous [ARCO] stages IIa to IIIc) who underwent the abovementioned hip-preserving surgeries between January 2003 and June 2012. The mean (range) follow-up times (years) were 12.9 (7–16) and 9.3 (6–16) in groups A and B, respectively. Clinical outcomes were assessed using the Harris Hip Score (HHS), visual analog scale (VAS) score, and forgotten joint score (FJS). A survival analysis was performed using the Kaplan-Meier method. The end point was THA. Groups A and B showed postoperative improvements, respectively, in HHS from 65 ± 7.2 to 80.3 ± 14.5 and from 66 ± 5.9 to 82.4 ± 13.6 (p 0.05) and 15-year survival rate (84.1% and 86%, respectively, p > 0.05) were found between groups A and B. Autologous and allogeneic fibular grafts can attain equally good clinical outcomes and high survival rates in long-term follow-up, and thus can greatly delay THA owing to good bone osseointegration and sufficient mechanical support. Notably, the ratio of failure will increase when patients were more than 37 years old. Level III, therapeutic study

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Topics: Survival rate (56%), Harris Hip Score (55%), Femoral head (51%)

1 Citations


Open accessJournal ArticleDOI: 10.1186/S13018-021-02614-Z
Yuzhu Wang1, Go Yamako1, Takato Okada1, Hideki Arakawa1  +2 moreInstitutions (1)
Abstract: Background Intertrochanteric curved varus osteotomy (CVO) has been widely used to remove the necrotic bone away from the weight-bearing portion in the treatment of osteonecrosis of the femoral head (ONFH). However, whether all types of necrosis will benefit from CVO, in terms of the stress level, the effect of different center-edge (CE) angles of acetabulum on stress distribution of necrosis after CVO, and the relationship between the intact ratio and the stress of necrosis, has never been addressed. The purpose of the study was to evaluate the influence of CVO on the stress reduction in necrotic bone using a finite element analysis (FEA) with different CE angles. Methods CVO finite element models of the hip joint were simulated with a lesion of 60°. The osteotomy angles were divided into four configurations (15°, 20°, 25°, and 30°), and three types (A, B, and C1) of lesions were established based on the Japanese Investigation Committee (JIC) classification. In addition, two CE angles (18° and 33°) of acetabulum were considered. The maximum and mean von Mises stress were analyzed in terms of the necrotic bone by a physiological loading condition. Moreover, the correlation of the intact ratio measured in 3D and the stress distribution after CVO was analyzed. Results Stress reduction was obtained after CVO. For type B, the CVO angle was 20° (0.61 MPa), and for type C1, the CVO angle was 30° (0.77 MPa), if the mean stress level was close to type A (0.61 MPa), as a standard. The maximum and mean von Mises stress were higher in the CE angle of 18°models, respectively. The intact ratio measured in 3D had a good negative correlation with stress after CVO and had more influence on stress distribution in comparison to other geometric parameters. Conclusions For making decisions about the biomechanics of CVO, a CVO angle of > 20° was recommended for type B and > 30° was safe for type C1. The risk of progressive collapse was increased in the insufficient situation of the weight-bearing portion after CVO. The intact ratio could provide information about clinical outcomes and stress distribution after CVO.

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Open accessJournal ArticleDOI: 10.1186/S13018-021-02332-6
Abstract: Osteonecrosis of the femoral head (ONFH) is a debilitating condition. Vascularized iliac bone graft (VIBG) is a joint-preserving surgery to improve blood supply to the avascular portion of the femoral head which may delay secondary osteoarthritis and total hip arthroplasty (THA). However, whether VIBG will affect the subsequent THA survivorship and outcomes are still uncertain. Implant survivorship and clinical outcomes were compared between 27 patients who had undergone prior VIBG and 242 patients who had only undergone THA for ONFH. Baseline characteristics and the postoperative Harris Hip Score (HHS) were also recorded and compared between the two groups. Implant survivorship was determined using Kaplan-Meier survival analysis. The overall implant survival for all patients who had a primary diagnosis of ONFH and eventually underwent THA was 92.9%. There was no significant difference in the implant survivorship between the group who directly received THA (survivorship of 93%) and the group which failed VIBG and was subsequently converted to THA (survivorship of 91.9%) (p = 0.71). In addition, higher THA revision rates were associated with smokers and drinkers. VIBG may be a reasonable option as a “buy-time” procedure for ONFH. Even if conversion to THA is eventually required, patients may be reassured that the overall survivorship and clinical outcomes may not be compromised. Patients are recommended to give up smoking and binge drinking prior to THA to increase implant survival rate.

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Topics: Harris Hip Score (56%), Survivorship curve (56%), Femoral head (52%) ... show more

References
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02 Apr 1999-Science
Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

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19,560 Citations



Journal ArticleDOI: 10.1002/JCB.20886
Arnold I. Caplan1, James E. Dennis1Institutions (1)
Abstract: Adult marrow-derived Mesenchymal Stem Cells (MSCs) are capable of dividing and their progeny are further capable of differentiating into one of several mesenchymal phenotypes such as osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon-ligament fibroblasts, and adipocytes. In addition, these MSCs secrete a variety of cytokines and growth factors that have both paracrine and autocrine activities. These secreted bioactive factors suppress the local immune system, inhibit fibrosis (scar formation) and apoptosis, enhance angiogenesis, and stimulate mitosis and differentiation of tissue-intrinsic reparative or stem cells. These effects, which are referred to as trophic effects, are distinct from the direct differentiation of MSCs into repair tissue. Several studies which tested the use of MSCs in models of infarct (injured heart), stroke (brain), or meniscus regeneration models are reviewed within the context of MSC-mediated trophic effects in tissue repair.

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2,559 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2007.08.025
19 Oct 2007-Cell
Abstract: The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.

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Topics: Hematopoietic stem cell niche (57.99%), Stromal cell (55%), Bone marrow (53%) ... show more

1,914 Citations


Open accessJournal ArticleDOI: 10.1634/STEMCELLS.19-3-180
01 May 2001-Stem Cells
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1,865 Citations


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