scholarly journals In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2

Blood ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 3635-3644 ◽  
Author(s):  
Ken Maes ◽  
Elizabeta Nemeth ◽  
G. David Roodman ◽  
Alissa Huston ◽  
Flavia Esteve ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Morphogenetic Proteins ◽  
Bone Morphogenetic Protein 2 ◽  
Minor Effect ◽  
Morphogenetic Protein ◽  
Huh7 Cells ◽  
Serum Hepcidin ◽  
Stimulatory Capacity ◽  
A Minor

Abstract Hepcidin is the principal iron-regulatory hormone and a pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. We showed that MM patients had increased serum hepcidin, which inversely correlated with hemoglobin, suggesting that hepcidin contributes to MM-related anemia. Searching for hepcidin-inducing cytokines in MM, we quantified the stimulation of hepcidin promoter-luciferase activity in HuH7 cells by MM sera. MM sera activated the hepcidin promoter significantly more than did normal sera. We then examined the role of bone morphogenetic proteins (BMPs) and interleukin-6 (IL-6), the major transcriptional regulators of hepcidin. Mutations in both BMP-responsive elements abrogated the activation dramatically, while mutations in the IL-6–responsive signal transducer and activator of transcription 3-binding site (STAT3-BS) had only a minor effect. Cotreatment with anti–BMP-2/4 or noggin-Fc blocked the promoter induction with all MM sera, anti–IL-6 blocked it with a minority of sera, whereas anti–BMP-4, -6, or -9 antibodies had no effect. BMP-2–immunodepleted MM sera had decreased promoter stimulatory capacity, and BMP-2 concentrations in MM sera were significantly higher than in normal sera. Our results demonstrate that BMP-2 is a major mediator of the hepcidin stimulatory activity of MM sera.

Role of mature leaves in inhibition of root bud growth inEuphorbia esulaL.

Weed Science ◽  
1999 ◽  
Vol 47 (5) ◽  
pp. 544-550 ◽  
Author(s):  
David P. Horvath
Keyword(s):  
Lateral Roots ◽  
Axillary Buds ◽  
Minor Effect ◽  
Correlative Inhibition ◽  
Auxin Transport Inhibitor ◽  
Naphthylphthalamic Acid ◽  
Bud Growth ◽  
A Minor ◽  
Root Buds

Earlier studies on the source of signals controlling correlative inhibition of root buds (underground adventitious buds located on the lateral roots) inEuphorbia esulaindicated that either growing meristems (apical or axillary buds) or fully expanded leaves could prevent root buds from breaking quiescence. An investigation of the production and transport requirements of the leaf-derived signal is described. As few as three leaves remaining on budless stems greatly reduced the growth of (but not the number of growing) root buds. Also, light and CO2fixation were necessary for the leaf effects on root bud growth, but not necessary for correlative inhibition imposed by growing axillary buds. Treatment of plants with Ametryn induced root bud growth on budless plants but not on plants with intact axillary buds. The polar auxin transport inhibitor N-1-naphthylphthalamic acid prevented transmission or the signal from growing axillary buds, but it had only a minor effect on the transmission of the leaf-derived signal. Treatment of plants with gibberellic acid (GA) induced growth of root buds under otherwise noninducing conditions to some extent in all plants. However, the greatest effects of GA were on plants with intact leaves (meristemless/budless and meristemless). GA had no significant effect on root bud quiescence under conditions that induced root bud growth.

Key role of the expression of bone morphogenetic proteins in increasing the osteogenic activity of osteoblast-like cells exposed to shock waves and seeded on bioactive glass-ceramic scaffolds for bone tissue engineering

2014 ◽  
Vol 29 (5) ◽  
pp. 728-736 ◽  
Author(s):  
Giuliana Muzio ◽  
Germana Martinasso ◽  
Francesco Baino ◽  
Roberto Frairia ◽  
Chiara Vitale-Brovarone ◽  
...  
Keyword(s):  
Shock Wave ◽  
Alkaline Phosphatase ◽  
Shock Waves ◽  
Bioactive Glass ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Proteins ◽  
Glass Ceramic ◽  
Osteogenic Activity ◽  
Morphogenetic Protein

In this work, the role of shock wave-induced increase of bone morphogenetic proteins in modulating the osteogenic properties of osteoblast-like cells seeded on a bioactive scaffold was investigated using gremlin as a bone morphogenetic protein antagonist. Bone-like glass-ceramic scaffolds, based on a silicate experimental bioactive glass developed at the Politecnico di Torino, were produced by the sponge replication method and used as porous substrates for cell culture. Human MG-63 cells, exposed to shock waves and seeded on the scaffolds, were treated with gremlin every two days and analysed after 20 days for the expression of osteoblast differentiation markers. Shock waves have been shown to induce osteogenic activity mediated by increased expression of alkaline phosphatase, osteocalcin, type I collagen, BMP-4 and BMP-7. Cells exposed to shock waves plus gremlin showed increased growth in comparison with cells treated with shock waves alone and, conversely, mRNA contents of alkaline phosphatase and osteocalcin were significantly lower. Therefore, the shock wave-mediated increased expression of bone morphogenetic protein in MG-63 cells seeded on the scaffolds is essential in improving osteogenic activity; blocking bone morphogenetic protein via gremlin completely prevents the increase of alkaline phosphatase and osteocalcin. The results confirmed that the combination of glass-ceramic scaffolds and shock waves exposure could be used to significantly improve osteogenesis opening new perspectives for bone regenerative medicine.

Osteolysis in Lumbar Interbody Fusions: The Role of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)

2012 ◽  
Vol 2 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Richard J Nasca
Keyword(s):  
Bone Morphogenetic Protein ◽  
Radicular Pain ◽  
Human Bone ◽  
Bone Morphogenetic Protein 2 ◽  
Idiosyncratic Reaction ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Dermatomal Level ◽  
Recombinant Human Bone

ABSTRACT Osteolysis may occur following lumbar interbody fusion procedures in which recombinant human bone morphogenetic protein-2, more commonly known as rhBMP-2, is used. The actual incidence of this process is unknown. Osteolysis results from an osteoclastic, rather than an osteoblastic response to rhBMP-2 and its carrier on trabecular vertebral bone, early in the sequence of bone graft healing. This osteoclastic response may represent an idiosyncratic reaction in those affected. The patient usually does well in the immediate postoperative period with resolution of their preoperative complaints of axial and radicular pain. However, at 4 to 12 weeks following the index surgery, the patient experiences a recurrence of severe back and radicular pain corresponding to the dermatomal level(s) operated upon. Laboratory studies including erythrocyte sedimentation rate, C reactive protein, and cultures are negative for infection. Imaging studies show areas of bone destruction and cyst formation containing fluid. In the majority of post-operative patients with osteolysis, there is an osteoblastic healing response with symptom resolution. Supportive, nonoperative care is usually effective in managing the patient. Nasca RJ. Osteolysis in Lumbar Interbody Fusions: The Role of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2). The Duke Orthop J 2012;2(1):50-54.

The role of bone morphogenetic protein-2 in vivo in regeneration of peripheral nerves

2007 ◽  
Vol 45 (3) ◽  
pp. 197-202 ◽  
Author(s):  
Yan-Liang Wang ◽  
Da-Zhang Wang ◽  
Xin Nie ◽  
De-Lin Lei ◽  
Yan-Pu Liu ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Peripheral Nerves ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1821-1828 ◽  
Author(s):  
D.M. Duprez ◽  
K. Kostakopoulou ◽  
P.H. Francis-West ◽  
C. Tickle ◽  
P.M. Brickell
Keyword(s):  
Gene Expression ◽  
Anterior Part ◽  
Ectopic Expression ◽  
Mirror Image ◽  
Limb Bud ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Wing Bud ◽  
Hoxd Gene

Bone morphogenetic protein-2 (BMP-2) has been implicated in the polarizing region signalling pathway, which specifies pattern across the antero-posterior of the developing vertebrate limb. Retinoic acid and Sonic Hedgehog (SHH) can act as polarizing signals; when applied anteriorly in the limb bud, they induce mirror-image digit duplications and ectopic Bmp-2 expression in anterior mesenchyme. In addition, the two signals can activate Fgf-4 expression in anterior ridge and HoxD expression in anterior mesenchyme. We tested the role of BMP-2 in this signalling cascade by ectopically expressing human BMP-2 (hBMP-2) at the anterior margin of the early wing bud using a replication defective retroviral vector, and found that ectopic expression of Fgf-4 was induced in the anterior part of the apical ectodermal ridge, followed later by ectopic expression of Hoxd-11 and Hoxd-13 in anterior mesenchyme. This suggests that BMP-2 is involved in regulating Fgf-4 and HoxD gene expression in the normal limb bud. Ectopically expressed hBMP-2 also induced duplication of digit 2 and bifurcation of digit 3, but could not produce the mirror-image digit duplications obtained with SHH-expressing cells. These results suggest that BMP-2 may be involved primarily in maintenance of the ridge, and in the link between patterning and outgrowth of the limb bud.

Formation of Painful Seroma and Edema After the Use of Recombinant Human Bone Morphogenetic Protein-2 in Posterolateral Lumbar Spine Fusions

Neurosurgery ◽  
2010 ◽  
Vol 66 (6) ◽  
pp. 1044-1049 ◽  
Author(s):  
Mark P. Garrett ◽  
Udaya K. Kakarla ◽  
Randall W. Porter ◽  
Volker K.H. Sonntag
Keyword(s):  
Bone Morphogenetic Protein ◽  
Operating Room ◽  
Bone Morphogenetic Proteins ◽  
Spine Surgery ◽  
Lumbar Fusion ◽  
Bone Morphogenetic Protein 2 ◽  
Posterolateral Lumbar Fusion ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Recombinant Human Bone

Abstract BACKGROUND The use of bone morphogenetic proteins for fusion augmentation in spine surgery has increased dramatically in recent years. Information is continually emerging regarding the effectiveness and safety profile of these compounds. OBJECTIVE We have noted an increased incidence in sterile seroma formation and painful edema after the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for posterolateral lumbar fusion. We present a retrospective review to determine the incidence of seroma formation and to discuss its clinical implications. METHODS We retrospectively reviewed the operative reports of patients who underwent posterolateral lumbar fusion with the addition of rhBMP-2. We identified all patients who required surgical exploration of a postoperative sterile seroma. RESULTS Of the 130 patients who underwent posterolateral lumbar fusion with rhBMP-2, 6 (4.6%) were returned to the operating room for exploration of a sterile seroma. The total amount of rhBMP-2 delivered to the posterolateral space per patient was 2.1 to 14.7 mg (mean, 8.4 mg per patient). The patients were returned to the operating room 5 to 13 days (mean, 7.7 days) after their initial surgery, and infection was ruled out in all cases by intraoperative cultures. CONCLUSION There seems to be an increased incidence of formation of sterile seroma and painful edema in the lumbar region after posterolateral fusion with rhBMP-2. This report, along with other series highlighting the potential complications of bone morphogenetic proteins, suggests that more caution should be used when these compounds are used. Further studies are required to better define the risks and benefits of using bone morphogenetic proteins for spine surgery.

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