scholarly journals Bone Morphogenetic Protein 4 Gene Therapy in Mice Inhibits Myeloma Tumor Growth, But Has a Negative Impact on Bone

JBMR Plus ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Marita Westhrin ◽  
Toril Holien ◽  
Muhammad Zahoor ◽  
Siv Helen Moen ◽  
Glenn Buene ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tumor Growth ◽  
Bone Morphogenetic Protein ◽  
Negative Impact ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein

scholarly journals Bone morphogenetic protein 4 gene therapy in mice inhibits myeloma tumor growth, but has a negative impact on bone

2019 ◽  
Author(s):  
Marita Westhrin ◽  
Toril Holien ◽  
Muhammad Zahoor ◽  
Siv Helen Moen ◽  
Glenn Buene ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Multiple Myeloma ◽  
Bone Formation ◽  
Tumor Growth ◽  
Trabecular Bone ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 4 ◽  
Myeloma Cells ◽  
Morphogenetic Protein ◽  
Virus Serotype

AbstractMultiple myeloma is characterized by accumulation of malignant plasma cells in the bone marrow. Most patients suffer from an osteolytic bone disease, caused by increased bone degradation and reduced bone formation. Bone morphogenetic protein 4 (BMP4) is important for both pre- and postnatal bone formation and induces growth arrest and apoptosis of myeloma cells. BMP4-treatment of myeloma patients could have the potential to reduce tumor growth and restore bone formation. We therefore explored BMP4 gene therapy in a human-mouse model of multiple myeloma where humanized bone scaffolds were implanted subcutaneously in RAG2−/−γC−/−mice. Mice were treated with adeno-associated virus serotype 8 BMP4 vectors (AAV8-BMP4) to express BMP4 in the liver. When mature BMP4 was detectable in the circulation, myeloma cells were injected into the scaffolds and tumor growth was examined by weekly imaging. Strikingly, the tumor burden was reduced in AAV8-BMP4 mice compared with the AAV8-CTRL mice, suggesting that increased circulating BMP4 reduced tumor growth. BMP4-treatment also prevented bone loss in the scaffolds, most likely due to reduced tumor load. To delineate the effects of BMP4 overexpression on bone per se, without direct influence from cancer cells, we examined the unaffected, non-myeloma femurs by μCT. Surprisingly, the AAV8-BMP4 mice had significantly reduced trabecular bone volume, trabecular numbers, as well as significantly increased trabecular separation compared with the AAV8-CTRL mice. There was no difference in cortical bone parameters between the two groups. Taken together, BMP4 gene therapy inhibited myeloma tumor growth, but also reduced the amount of trabecular bone in mice. Our data suggest that care should be taken when considering using BMP4 as a therapeutic agent.

A Role for Bone Morphogenetic Protein-4 in Lymph Node Vascular Remodeling and Primary Tumor Growth

2011 ◽  
Vol 71 (20) ◽  
pp. 6547-6557 ◽  
Author(s):  
Rae H. Farnsworth ◽  
Tara Karnezis ◽  
Ramin Shayan ◽  
Masataka Matsumoto ◽  
Cameron J. Nowell ◽  
...  
Keyword(s):  
Lymph Node ◽  
Tumor Growth ◽  
Bone Morphogenetic Protein ◽  
Primary Tumor ◽  
Vascular Remodeling ◽  
Bone Morphogenetic Protein 4 ◽  
Primary Tumor Growth ◽  
Morphogenetic Protein

In vivo bone formation in fracture repair induced by direct retroviral-based gene therapy with bone morphogenetic protein-4

Bone ◽  
2003 ◽  
Vol 32 (6) ◽  
pp. 591-601 ◽  
Author(s):  
Charles H Rundle ◽  
Naohisa Miyakoshi ◽  
Yuji Kasukawa ◽  
Shin-Tai Chen ◽  
Matilda H.-C Sheng ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Fracture Repair ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein ◽  
In Vivo Bone Formation

scholarly journals Identification of bone morphogenetic protein 4 in the saliva after the placement of fixed orthodontic appliance

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lovorka Grgurevic ◽  
Ruder Novak ◽  
Grgur Salai ◽  
Vladimir Trkulja ◽  
Lejla Ferhatovic Hamzic ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Protein ◽  
Bone Remodeling ◽  
Small Sample ◽  
Central Position ◽  
Published Data ◽  
Bone Morphogenetic Protein 4 ◽  
Orthodontic Appliance ◽  
Morphogenetic Protein ◽  
Fixed Orthodontic Appliance

Abstract Background This study was conducted in order to explore the effects of orthodontic tooth movement (OTM) on the changes of salivary proteome. This prospective observational pilot study recruited 12 healthy teenage boys with malocclusion treated with a fixed orthodontic appliance and 6 appropriate control participants. Saliva samples were collected a day before and at 0, 2, 7, and 30 days after initialization of treatment, corresponding to the initial, lag, and post-lag phases of OTM. Pooled samples were analyzed by liquid chromatography-mass spectrometry, ELISA, and Western blotting. To date, there is no published data on the presence of BMP molecules or their antagonists in the saliva or in the gingival cervical fluid related to orthodontic conditions. Results A total of 198 identified saliva proteins were classified based on their functional characteristics. Proteins involved in bone remodeling were observed exclusively 30 days post appliance placement, including bone morphogenetic protein 4 (BMP4), a BMP antagonist BMP-binding endothelial regulator, insulin-like growth factor-binding protein 3, cytoskeleton-associated protein 4, and fibroblast growth factor 5. Based on the analysis of protein interactions, BMP4 was found to have a central position in this OTM-related protein network. Conclusions The placement of a fixed orthodontic appliance induced occurrence of proteins involved in bone remodeling in the saliva at a time corresponding to the post-lag period of OTM. Limitations of this study include a relatively small sample size, limited time of monitoring patients, and the lack of interindividual variability assessment.

Expression of mRNA of murine bone-related proteins in ectopic bone induced by murine bone morphogenetic protein-4

1994 ◽  
Vol 277 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Seiichi Hirota ◽  
Kunio Takaoka ◽  
Jun Hashimoto ◽  
Takanobu Nakase ◽  
Teiji Takemura ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein ◽  
Ectopic Bone ◽  
Related Proteins
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