Proteasome function is required for platelet production

Shi, Dallas; Smith, Madeline; Campbell, Robert A.; Zimmerman, Patrick W.; Franks, Zechariah B.; Kraemer, Bjorn F.; Machlus, Kellie R.; Jing, Ling; Kamba, Patrick; Schwertz, Hansjörg; Rowley, Jesse W.; Miles, Rodney R.; Liu, Zhi Jian; Sola‐Visner, Martha; Italiano, Joseph E.; Christensen, Hilary; Kahr, Walter H.A.; Li, Dean Y.; Weyrich, Andrew S.

doi:10.1172/jci75247

Cited by 60 publications

(55 citation statements)

References 51 publications

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“…Proplatelet formation was studied in mouse bone marrow-derived megakaryocytes as described recently (73). Mice (8 to 10 weeks of age) were euthanized, and cells were obtained from the bone marrow of femurs and tibias.…”

Section: Differentiation Of Mouse Megakaryocytesmentioning

confidence: 99%

RASA3 is a critical inhibitor of RAP1-dependent platelet activation

Paul²,

et al. 2015

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Section: Differentiation Of Mouse Megakaryocytesmentioning

confidence: 99%

RASA3 is a critical inhibitor of RAP1-dependent platelet activation

Paul²,

et al. 2015

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“…As known, zoledronic acid is clearly effective at inhibiting the development of myeloma bone disease, but the exact mechanism of its anti-MM action is still unexplained. There are different hypothesis: it has been proposed that because less bone is destroyed following bisphosphonate treatment, there is less volume available for tumor expansion [2][3][4][5][6][7][8][9][10][11].…”

Section: Discussionmentioning

confidence: 99%

“…The authors propose that this effect is mediated by a complex interaction of increased pro-apoptotic factors and decreased cell cycle proteins. About the use of zoledronic acid in solid tumor, Santini et al [4] reported that in patients with advanced solid cancer and bone metastasis, pamidronate [2] and zoledronic acid [4][5][6][7][8][9][10][11][12][13] showed antiangiogenic properties which were associated with a significant and long-lasting decrease of VEGF serum levels following bisphosphonates infusion. These observations were later confirmed by Ferretti et al [14] who observed a transient but significant reduction of VEGF and bFGF, 48 hours after the infusion of zoledronic acid in breast cancer patients with bone metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Annibali¹,

Petrucci²,

Tirindelli³

et al. 2017

J Blood Lymph

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Objective: Multiple Myeloma (MM) is characterized by uncoupling of bone resorption from bone formation which leads to the predominance of resorption. Bisphosphonates are chemical compounds that selectively concentrate at the interface of the active osteoclasts and the bone resorption surface where they inhibit osteoclast activity. Aim of this study was to describe cytokines behaviour in MM and to evaluate whether zoledronic acid could have an in vivo anti-angiogenic property in MM as observed in solid tumours.Methods: Serum samples from 29 (16 males and 13 females) consecutive MM patients with lytic bone lesions treated with 4 mg of zoledronic acid were tested for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF α) and insulin growth factor (IGF-I). Basal cytokine levels were compared with the values observed after 1, 2, 7 and 21 days of treatment, using the Wilcoxon's test for nonparametric-dependent continuous variables.Results: A significant increase in IL-6 and TNF α was observed on days 1 and 2. As for VEGF, the levels of this cytokine did not change significantly from basal values during the entire period of observation except for a significant increase day 7 (P=0.0005). Moreover, PDGF significantly decreased (P=0.005) after 2 days from zoledronic acid infusion. Conclusions:From this study appears that in MM, treatment with zoledronic acid induces a transient reduction in PDGF according with previous studies in solid cancer, while the increase of IL-6 and VEGF could be related through a paracrine mechanism. The anti-myeloma effect of this drug could be driven through this mechanism.

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“…Emerging tools, technologies, and model systems may facilitate future studies. For example, genetically manipulated human CD34 + -derived megakaryocytes that form proplatelets, 17 lineage-restricted gene knockouts (eg, PF4-Cre murine models 18 ), and engineered genetic models using the CRISPR/Cas system 19 are just some of the exciting tools now available to dissect these mechanisms. Furthermore, transcriptome and proteome analysis of these targeted murine models using RNA deep sequencing 20,21 may guide us toward new unrecognized targets for future atherosclerosis research projects.…”

Section: Arfmentioning

confidence: 99%