scholarly journals Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin-4′-sulfonate on Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through AMPK-Mediated PPARγ Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Jung Hwan Oh ◽  
Fatih Karadeniz ◽  
Jung Im Lee ◽  
Youngwan Seo ◽  
Mi-Soon Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lipid Accumulation ◽  
Sulfonic Acid ◽  
Bone Marrow Cells ◽  
Adipogenic Differentiation ◽  
Polymerase Chain Reaction Analysis ◽  
Hydroxyl Group ◽  
Osteoporotic Bone ◽  
Ampk Activation ◽  
Beneficial Effects

Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties.

scholarly journals Multiple Myeloma Cells Alter Adipogenesis, Increase Senescence-Related and Inflammatory Gene Transcript Expression, and Alter Metabolism in Preadipocytes

2021 ◽  
Vol 10 ◽  
Author(s):  
Heather Fairfield ◽  
Samantha Costa ◽  
Carolyne Falank ◽  
Mariah Farrell ◽  
Connor S. Murphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Lipid Accumulation ◽  
Expression Profiles ◽  
Adipogenic Differentiation ◽  
Gene Expression Profiles ◽  
Mouse Bone Marrow ◽  
Gene Transcript ◽  
Bone Marrow Mscs

Within the bone marrow microenvironment, mesenchymal stromal cells (MSCs) are an essential precursor to bone marrow adipocytes and osteoblasts. The balance between this progenitor pool and mature cells (adipocytes and osteoblasts) is often skewed by disease and aging. In multiple myeloma (MM), a cancer of the plasma cell that predominantly grows within the bone marrow, as well as other cancers, MSCs, preadipocytes, and adipocytes have been shown to directly support tumor cell survival and proliferation. Increasing evidence supports the idea that MM-associated MSCs are distinct from healthy MSCs, and their gene expression profiles may be predictive of myeloma patient outcomes. Here we directly investigate how MM cells affect the differentiation capacity and gene expression profiles of preadipocytes and bone marrow MSCs. Our studies reveal that MM.1S cells cause a marked decrease in lipid accumulation in differentiating 3T3-L1 cells. Also, MM.1S cells or MM.1S-conditioned media altered gene expression profiles of both 3T3-L1 and mouse bone marrow MSCs. 3T3-L1 cells exposed to MM.1S cells before adipogenic differentiation displayed gene expression changes leading to significantly altered pathways involved in steroid biosynthesis, the cell cycle, and metabolism (oxidative phosphorylation and glycolysis) after adipogenesis. MM.1S cells induced a marked increase in 3T3-L1 expression of MM-supportive genes including Il-6 and Cxcl12 (SDF1), which was confirmed in mouse MSCs by qRT-PCR, suggesting a forward-feedback mechanism. In vitro experiments revealed that indirect MM exposure prior to differentiation drives a senescent-like phenotype in differentiating MSCs, and this trend was confirmed in MM-associated MSCs compared to MSCs from normal donors. In direct co-culture, human mesenchymal stem cells (hMSCs) exposed to MM.1S, RPMI-8226, and OPM-2 prior to and during differentiation, exhibited different levels of lipid accumulation as well as secreted cytokines. Combined, our results suggest that MM cells can inhibit adipogenic differentiation while stimulating expression of the senescence associated secretory phenotype (SASP) and other pro-myeloma molecules. This study provides insight into a novel way in which MM cells manipulate their microenvironment by altering the expression of supportive cytokines and skewing the cellular diversity of the marrow.

scholarly journals THE VALUE OF PENICILLIN IN THE TREATMENT OF AGRANULOCYTOSIS CAUSED BY THIOURACIL

Blood ◽  
1946 ◽  
Vol 1 (1) ◽  
pp. 53-66 ◽  
Author(s):  
MARY CATHERINE TYSON ◽  
PETER VOGEL ◽  
NATHAN ROSENTHAL
Keyword(s):  
Bone Marrow ◽  
Antibacterial Agents ◽  
Bone Marrow Cells ◽  
The Body ◽  
Bacterial Invasion ◽  
Beneficial Effects ◽  
Penicillin Therapy ◽  
History Of ◽  
Per Se ◽  
Hemopoietic System

Abstract Thiouracil has been found to be an effective drug in the treatment of hyperthyroidism. Agranulocytosis following its use occurred in nine cases, four of which terminated fatally. In five others a complete and rapid recovery took place following penicillin therapy. The latter drug is believed to be ideal for all cases of agranulocytosis, and especially those in which chemotherapy has been used and may have been responsible for the condition. Thus far we have not seen any report of any untoward effect on the hemopoietic system from the use of penicillin. The use of antibacterial agents for the treatment of agranulocytosis was suggested by Dameshek and Wolfson21 in 1942. It was believed by these authors that patients with agranulocytosis died not of the leukopenia per se but of the sepsis which developed secondarily to the lack of granulocytes. Two very severe cases of aminopyrine agranulocytosis treated with sulfathiazole made complete recoveries. For the treatment of sulfonamide agranulocytosis, it was suggested that a preparation differing from that which had already been used be given. With the discovery of penicillin, and its complete lack of possible deleterious effect on the bone marrow, its use was suggested by Dameshek17 (1944). A report on the beneficial effects of this medication in a case of sulfonamide agranulocytosis was later reported by Dameshek and Knowlton18 and similar cases by Sprague and Ferguson19 and by Meredith and Fink.20 Since sulfonamides may cause further toxic effect on the bone marrow, we feel that their use should be avoided in the treatment of agranulocytosis, especially where a history of previous use is obtained. We do not agree with others21, 22 who continue the use of sulfonamides in the treatment of leukopenia or agranulocytosis where these very drugs may have been responsible for the condition. It would seem better judgment to use penicillin, which by combating the bacterial invasion of the body and the consequent toxemia enables the patient to survive until the bone marrow cells regenerate.

scholarly journals Effect of Quercetin 3-O-β-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8044
Author(s):  
Jung Hwan Oh ◽  
Fatih Karadeniz ◽  
Youngwan Seo ◽  
Chang-Suk Kong
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Adipogenic Differentiation ◽  
Bmp Signaling ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differentiation Markers ◽  
Beneficial Effects

Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.

Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells

Bone ◽  
2008 ◽  
Vol 43 (3) ◽  
pp. 613-620 ◽  
Author(s):  
Kunitaka Menuki ◽  
Toshiharu Mori ◽  
Akinori Sakai ◽  
Miyuki Sakuma ◽  
Nobukazu Okimoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteoblast Differentiation ◽  
Bone Marrow Cells ◽  
Adipogenic Differentiation ◽  
High Expression ◽  
Pthrp Receptor ◽  
Marrow Cells

Proliferation of primitive myeloid progenitors can be reversibly induced by HOXA10

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3301-3308 ◽  
Author(s):  
Jon Mar Björnsson ◽  
Elisabet Andersson ◽  
Patrik Lundström ◽  
Nina Larsson ◽  
Xiufeng Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Target Genes ◽  
Bone Marrow Cells ◽  
Polymerase Chain Reaction Analysis ◽  
Hematopoietic Progenitors ◽  
Tetracycline Transactivator ◽  
Human Cd34 ◽  
Marrow Cells ◽  
Myeloid Progenitors

Abstract Recent studies show that several Hox transcription factors are important for regulation of proliferation and differentiation in hematopoiesis. Among these is H0XA10, which is selectively expressed at high levels in the most primitive subpopulation of human CD34+ bone marrow cells. When overexpressed, H0XA10 increases the proliferation of early progenitor cells and can lead to the development of myeloid leukemia. To study the effects of H0XA10 on primitive hematopoietic progenitors in more detail, transgenic mice were generated with regulatable H0XA10 expression. The transgenic mouse model, referred to as tetO-HOXA10, contains theH0XA10 gene controlled by a tetracycline-responsive element and a minimal promoter. Thus, the expression of H0XA10 is inducible and reversible depending on the absence or presence of tetracycline or its analog, doxycycline. A retroviral vector containing the tetracycline transactivator gene (tTA) was used to induce expression of the H0XA10 gene in bone marrow cells from the transgenic mice. Reverse transcription–polymerase chain reaction analysis confirmed regulatable H0XA10 expression in several transgenic lines. H0XA10 induction led to the formation of hematopoietic colonies containing blastlike cells and megakaryocytes. Moreover, the induction of H0XA10 resulted in significant proliferative advantage of primitive hematopoietic progenitors (spleen colony-forming units [CFU-S12]), which was reversible on withdrawal of induction. Activation of H0XA10 expression intet0-H0XA10 mice will therefore govern proliferation of primitive myeloid progenitors in a regulated fashion. This novel animal model can be used to identify the target genes of HOXA10 and better clarify the specific role of HOXA10 in normal and malignant hematopoiesis.

scholarly journals Ligustrum Japonicum fructus Induces Anti-adipogenetic and Pro-osteoblastogenic Activities in Human Bone Marrow-derived Mensencymal Stem Cells (P06-016-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
JungHwan Oh ◽  
Fatih Karadeniz ◽  
JungIm Lee ◽  
Youngwan Seo ◽  
Chang-Suk Kong
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Lipid Accumulation ◽  
Osteoblast Differentiation ◽  
Adipogenic Differentiation ◽  
Dependent Manner ◽  
Cellular Lipid ◽  
Protein Levels ◽  
Alp Activity ◽  
Ligustrum Japonicum

Abstract Objectives Masenchymal stem cells (MSCs) have pluripotent differentiation properties that confirmed to differentiate into myocyte, adipocyte, osteoblast, neuron and chondrocyte when specific culture conditions and stimuli are applied. In bone, both adipocytes and osteoblasts are derived from bone marrow MSCs (BMSCs) and production of these cells has been reported as reciprocal processes. The bone mass disequilibrium causes osteoporosis, as a result of elevated adipogenic differentiation accompanied by reducing bone formation. Therefore, in this study the effect of Ligustrum japonicum fructus (Waxleaf privet) on the adipogenesis and osteoblast differentiation was investigated in BMSCs. Methods The fruits of L. japonicum were extracted with dichloromethane and methanol, and the combined extracts were concentrated. Differentiation of BMSCs was performed by changing the medium into adipocyte and osteoblast differentiation supplied by Promocell GmbH. The cellular lipid was stained with Oil Red O and the alkaline phosphatase (ALP) activity was measured using a colormetric assay kit (Biovision, Inc.). The relative protein levels were measured by immunoblotting assay. Results Presense of L. japonicum fructus extract (LJE) inhibited the cellular lipid accumulation in a dose-dependent manner. Consistent with the effects on lipid accumulation, the adipocyte specific genes including PPARγ, C/EBPα and SREBP1c was down regulated by treatment with LJE. Moreover, treatment with LJE enhanced osteoblast differentiation observed as increased ALP activity and upregulated the proteALP, BMP-2 and osteocalcine protein levels. Conclusions The results indicated that LJE may prevent bone loss by inhibiting adipogenesis while activating the osteogenic differentiation in BMSCs. Therefore, LJE possess the potential to be utilized as a source of nutraceutical agents against osteoporosis. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP).

Addition of a second, different allogeneic graft accelerates white cell and platelet engraftment after T-cell–depleted bone marrow transplantation

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2235-2240 ◽  
Author(s):  
Benny J. Chen ◽  
Xiuyu Cui ◽  
Nelson J. Chao
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Cord Blood ◽  
Marrow Transplantation ◽  
Bone Marrow Cells ◽  
Cord Blood Transplantation ◽  
Beneficial Effects ◽  
Blood Transplantation ◽  
Cell Counts

Abstract Significant delays in engraftment and lymphoid recovery are the 2 major challenges in cord blood transplantation. The cause for this delay is presumed to be the low numbers of hematopoietic precursors found in one unit of cord blood. One approach to increase the stem cell doses could be to combine cord blood units from different donors differing at the major histocompatibility complex (MHC). As a first step toward this goal, the kinetics of hematologic engraftment and immune reconstitution were compared between 1 unit (2.5 × 106 cells) of T-cell–depleted bone marrow cells from a single donor (C57BL/6 [H2b] or SJL/J [H2s]) and 2 units from different donors (C57BL/6 + SJL/J) after transplantation into lethally irradiated (8.5 Gy) BALB/c recipients (H2d). Addition of T-cell–depleted bone marrow from an MHC-mismatched allogeneic donor doubled the white blood counts compared with recipients of one single unit on days +10 and +14. Similar effects were also observed on platelets. The beneficial effect of additional cells on peripheral T-cell counts were first observed on day +14. Cells both from donors (C57BL/6 and/or SJL/J) and recipients (BALB/c) contributed to myeloid and lymphoid reconstitution. The chimeras containing cells from 3 strains of mice were able to mount a recall immune response. Our data suggest that combining stem cells from MHC-mismatched allogeneic donors is feasible, that it has beneficial effects on myeloid engraftment and T-cell phenotypic recovery, and that the long-term stable mixed chimeras are immunologically normal following T-cell–depleted bone marrow transplantation.

Growth and adipogenic differentiation of mesenchymal stromal bone marrow cells during culturing in 3D macroporous agarose cryogel sponges

2008 ◽  
Vol 146 (1) ◽  
pp. 129-132 ◽  
Author(s):  
Yu. A. Petrenko ◽  
A. Yu. Petrenko ◽  
L. G. Damshkaln ◽  
N. A. Volkova ◽  
V. I. Lozinsky
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Adipogenic Differentiation ◽  
Marrow Cells

Human Bone Marrow MSC Transformation in Different Culture Conditions.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4253-4253
Author(s):  
Riccardo Saccardi ◽  
Serena Urbani ◽  
Benedetta Mazzanti ◽  
Simone Dal Pozzo ◽  
Susanna Benvenuti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Setting ◽  
Bone Marrow Cells ◽  
Adipogenic Differentiation ◽  
White Blood Cells ◽  
Flow Cytometric Analysis ◽  
Culture Conditions ◽  
Proliferation Rate ◽  
Complete Medium ◽  
Spontaneous Transformation

Abstract Human mesenchymal stem cells (MSC) have been isolated from different sources, expanded and characterized extensively. Their plasticity and immunomodulatory properties made these cells extremely promising in the fields of immunotherapy and regenerative medicine. Both safety and modality of preparation in a clinical setting are still be defined. We generated human MSC from normal donors bone marrow cells following 2 different isolation methods and culture conditions: white blood cells (buffy-coat) were plated in IMDM with gentamycin, 10% FBS and 2% Ultroser® G. Half of the complete medium was changed after one week and then the whole medium was added every 3–4 days. When approximately 80% of the flask surface was covered, the adherent cells were trypsinized and re-suspended in complete medium. mononucleated cells (MNC) purification by Ficoll density gradient separation and cultivation in DMEM-Low Glucose supplemented with 10% FBS and 1% antibiotic-antimycotic solution. Complete medium was changed after 3 days. When the cultures were near confluence, the cells were detached and replated. In both protocols, the isolated MSC (P0) were characterized by the number of Colony Forming Units-Fibroblasts (CFU-F), osteogenic and adipogenic differentiation, and immunophenotype based on the following monoclonal antibodies: CD34, CD45, CD14 (in order to quantify hematopoietic and monocytic contamination); CD29, CD44, CD166, CD90, CD73, HLA-DP DQ DR, HLA-ABC and CD105. We observed a spontaneous transformation of MSC in 6/29 cases (20%), irrespective of the isolation and expansion protocols and the cells showed a different morphologic, immunophenotypic, proliferative and cytogenetic pattern. In particular, cells assumed uniform cuboidal and round morphology and lost their spindle shaped aspect. MSC transformation usually occurred after the 4th passage in culture; only once it occurred after only one passage in culture (P1). Flow cytometric analysis showed a complete down regulation of MSC surface markers such as CD73, CD105, CD166, CD90, CD44, CD29, HLA ABC. The typical biparametric FSC/SSC distribution of RS cells and mMSC was lost as well. Transformed MSC showed very low expression of KDR, Ulex and vWF. Differentiation capability of the transformed cells was also lost and only small areas stained positive for classic differentiation tests (Oil Red O for adipogenic and Alizarin S for osteogenic differentiation). Cytogenetic analysis showed aneuploidy and a wide pattern of chromosomal aberrations. These cells also showed a high level of telomerase activity when compared with non-transformed MSC. Finally, their proliferation rate was greatly increased. CONCLUSIONS: we observed spontaneous transformation of MSC generated under various conditions. We speculate that this phenomenon might be related to the high proliferation rate in culture of cells still retaining a rather undifferentiated pattern. Further investigations about the transformation modality and its biological pathways are needed. The use of these cells in a clinical setting should be adequately evaluated for safety reasons.

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