Bone remodeling alterations in myelodysplastic syndrome

Mellibovsky, Leonardo; Díez, Adolfo; Serrano, Sergi; Aubia, J; Pérez-Vila, Encarna; Mariñoso, M.L.; Nogués, Xavier; Recker, Robert R.

doi:10.1016/s8756-3282(96)00210-4

Cited by 31 publications

(24 citation statements)

References 25 publications

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“…Osteocalcin was found to be increased in our study, independently of the near normal levels of PTH. The increased concentration of osteocalcin is in agreement with the observations made by Mellibovsky et al [8], as the higher levels of osteocalcin may be responsible for the disruption in bone acquisition. Studies have demonstrated the coexpression of CD117 (c-kit) and osteocalcin in activated bone marrow stem cells in hematological diseases.…”

Section: Discussionsupporting

confidence: 92%

“…Osteocalcin acts as a negative regulator of osteosynthesis, increasing bone resorption by osteoclasts. A study of the histomorphometry of bone biopsies from MDS patients by Mellibovsky et al [8] revealed a disrupted bone function with reduced osteosynthesis and a loss of osteoclast population as a result of the overall derangement in the environment of the bone marrow. Osteocalcin was found to be increased in our study, independently of the near normal levels of PTH.…”

Section: Discussionmentioning

confidence: 99%

“…Osteoblasts are prominent components of the HSC niche and developmentally have the capacity to produce a vast array of cytokines which are important for several hematopoietic pathways, including proliferation of hematopoietic progenitors. In several situations in which bone remodeling is compromised, hematopoiesis is also compromised [8]. Hematopoiesis was shown to be severely affected in mice with osteoblast deficiency, indicating a stimulating role of the osteoblast in the homeostasis of HSCs [9].…”

Section: Introductionmentioning

confidence: 99%

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Metabolism-Related Cytokine and Hormone Levels in the Serum of Patients with Myelodysplastic Syndromes

et al. 2013

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Background: A number of cytokines secreted from the bone marrow stromal cells and circulating hormones related to bone, adipose tissue and glucose metabolism might be involved in the pathogenesis of myelodysplastic syndromes (MDS). Methods: Serum levels of cytokines related to the metabolism of bone tissue [osteocalcin and parathyroid hormone (PTH)], adipose tissue (adiponectin, leptin and ghrelin) and glucose [insulin and insulin-like growth factor-1 (IGF-1)] were determined in 72 patients suffering from MDS, mostly of the low-risk group according to FAB classification, and 41 healthy individuals (controls). Results: Adiponectin and osteocalcin serum levels were significantly elevated in the MDS patients. Leptin, insulin and IGF-1 serum levels were reduced. No difference was found in the serum levels of PTH and ghrelin. Leptin levels were reversibly associated with patient blast count. Conclusion: Increased serum levels of adiponectin and low levels of IGF-1 in MDS patients may counterbalance the increased rate of apoptosis in the pool of hematopoietic progenitors. Osteocalcin secreted by osteoblasts regulates the renewal and proliferation of hematopoietic stem cells. Hormones and cytokines either secreted by the cells of the bone marrow stroma or transferred by the microcirculation act on hematopoietic progenitors and may regulate their differentiation, apoptosis and proliferation rate in MDS.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolism-Related Cytokine and Hormone Levels in the Serum of Patients with Myelodysplastic Syndromes

et al. 2013

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“…24 MDS-MSC showed various degrees of osteogenic differentiation, while the adipogenic potential was significantly lower in all MDS groups than in healthy controls. Mellibovsky et al showed that MDS patients have a typical adynamic bone with decreased mineral deposition 31 and a recent study by Raaijmakers demonstrated how Dicer1 deletion in mice osteoprogenitors leads to bone dysfunction and development of MDS that progresses to AML. 10 Varga et al 25 previously described similar defective adipogenic differentiation in MDS-MSC.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cells from patients with myelodyplastic syndrome display distinct functional alterations that are modulated by lenalidomide

et al. 2013

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ABSTRACTtypes including MDS associated with single del(5q), and characterized their clonogenicity and differentiation potential. Methods Human samplesTwenty MDS patients were studied; their characteristics are detailed in Online Supplementary Table S1. Our control cohort consisted of one male and five female healthy individuals undergoing orthopedic surgery with a median age of 60 years (range, 56-65). MSC were obtained as previously described. 18 Patients were classified for the study as "lower risk" with and without del(5q) (LR, LR-5q ) (<5% bone marrow blasts and IPSS-low/int-1), and as "higher-risk" (HR) (>5% bone marrow blasts and IPSS-int-2/high). Magnetically sorted HSPC were obtained from peripheral blood of healthy individuals after mobilization. Samples were collected after approval by our Institutional Review Board, and written informed consent was obtained. A detailed description is available in the Online Supplementary Material. Lenalidomide treatmentLEN was kindly provided by Celgene (Munich, Germany) and prepared using 10% dimethyl-sulfoxide as a vehicle. The experiments were performed with 0.1 μM and 1 μM of the drug. Characterization of the mesenchymal stromal cellsClonality, self-renewal, generation of single cell-derived colonies (SCD), expression of cell surface and adhesion molecules with flow cytometry, differentiation potential, proliferation, viability, apoptosis, senescence, and cell cycle were studied. Detailed information about the experiments is provided in the Online Supplementary Material. Co-culture of myelodysplastic syndrome-mesenchymal stromal cells with hematopoietic stem and progenitor cells, clonogenicity and apoptosis assayThe capacity of MSC to support HSPC was tested using a 4-week cobblestone area-forming (CAF-C) assay and a 14-day colony-forming unit granulocyte-erythrocytemonocyte/macrophage (CFU-GEMM) assay as described in the Online Supplementary Material. HSPC or the cell line KG1-α were labeled with carboxyfluorescein-diacetate-succinimidyl-ester (CFSE) prior to co-culture with MSC for 72 h, or left unlabeled and co-cultured for 24 h, with or without the addition of 100 nM recombinant tumor necrosis factor alpha (TNF-α, Peprotech). Apoptosis and proliferation were studied by annexin-V staining and CFSE dilution using flow cytometry. Cytokine measurement and transwell migration assaySupernatant from MSC was obtained after culture with or without LEN and used for enzyme-linked immunoabsorbent assay (ELISA) determinations of SDF-1α, angiopoietin-1 (ANG1), and stem cell factor (SCF) levels. Supernatant was also used for a 4-h transwell migration assay with 1x10 5 HSPC, as described previously. 18 The CXCR4 antagonist AMD3100 (Sigma) was used at a concentration of 10 μM.RNA extraction, complementary DNA synthesis and real time polymerase chain reaction mRNA extracted with Trizol reagent (Invitrogen) was transcribed into complementary-DNA and used for real time polymerase chain reaction (RT-PCR) analysis for fatty acid binding protein 4 (FABP4), SDF-1α , ANG1, and SCF. Ab...

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“…ABD is common among the elderly [9, 10, 12, 14, 21, 42, 64, 78, 79], after renal transplantation [80, 81, 82]and even in myelodysplastic patients without uremia [83]. ABD is common in the predialysis uremic population, with an incidence of 12–48% [21, 43, 78, 84, 85, 86, 87], even in the absence of concurrent vitamin D and calcium therapy [79, 88].…”

Section: An Iatrogenic Disease?mentioning

confidence: 99%

Causes and Consequences of Adynamic Bone Disease

Heaf¹

2001

Nephron

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Bone remodeling alterations in myelodysplastic syndrome

Cited by 31 publications

References 25 publications

Metabolism-Related Cytokine and Hormone Levels in the Serum of Patients with Myelodysplastic Syndromes

Metabolism-Related Cytokine and Hormone Levels in the Serum of Patients with Myelodysplastic Syndromes

Mesenchymal stromal cells from patients with myelodyplastic syndrome display distinct functional alterations that are modulated by lenalidomide

Causes and Consequences of Adynamic Bone Disease

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