scholarly journals Combinatorial gene therapy for bone regeneration: Cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2, 4, and 7

2005 ◽  
Vol 95 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Ming Zhao ◽  
Zhuoran Zhao ◽  
Jeong-Tae Koh ◽  
Taocong Jin ◽  
Renny T. Franceschi
1997 ◽  
Vol 57 (1-3) ◽  
pp. 19-25 ◽  
Author(s):  
Marielle Christ ◽  
Monika Lusky ◽  
Fabienne Stoeckel ◽  
Dominique Dreyer ◽  
Annick Dieterlé ◽  
...  

2001 ◽  
Vol 3 (4) ◽  
pp. 449-461 ◽  
Author(s):  
Ioannis K. Moutsatsos ◽  
Gadi Turgeman ◽  
Shuanhu Zhou ◽  
Basan Gowda Kurkalli ◽  
Gadi Pelled ◽  
...  

Gene Therapy ◽  
2003 ◽  
Vol 10 (24) ◽  
pp. 2013-2019 ◽  
Author(s):  
S C-N Chang ◽  
H L Chuang ◽  
Y R Chen ◽  
J K Chen ◽  
H-Y Chung ◽  
...  

1993 ◽  
Vol 3 (3) ◽  
pp. 499-503 ◽  
Author(s):  
Karen F. Kozarsky ◽  
James M. Wilson

2018 ◽  
Vol 7 (10) ◽  
pp. 548-560 ◽  
Author(s):  
I. Qayoom ◽  
D. B. Raina ◽  
A. Širka ◽  
Š. Tarasevičius ◽  
M. Tägil ◽  
...  

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


2002 ◽  
Vol 76 (4) ◽  
pp. 1559-1568 ◽  
Author(s):  
Lee Anne Tibbles ◽  
Jason C. L. Spurrell ◽  
Gloria P. Bowen ◽  
Qiang Liu ◽  
Mindy Lam ◽  
...  

ABSTRACT The use of adenovirus vectors for human gene therapy is limited by potent inflammatory responses that result in significant morbidity. In kidney-derived epithelial cells (REC), activation of extracellular signal-regulated kinase 1/2 (ERK) and p38 kinase (p38) pathways occurred within 20 min of transduction with the serotype 5 adenovirus vector AdCMVβgal. Inhibition of ERK and p38 with U0126 and SB203580, respectively, reduced the expression of IP-10 mRNA following transduction with AdCMVβgal. To determine the role of the coxsackievirus-adenovirus receptor (CAR) or αv integrins in the activation of ERK and p38 and the expression of IP-10, REC cells were transduced with the fiber-modified and RGD-deleted adenovirus vectors AdL.F(RAEK-HA) and AdL.PB(HA), respectively. Compared with the wild-type capsid vector Ad5Luc, transduction with AdL.F(RAEK-HA) and AdL.PB(HA) resulted in reduced ERK-p38 activation and less IP-10 mRNA expression. The decreased IP-10 expression induced by the tropism-modified vectors was due to diminished transduction, since increasing multiplicity of infection resulted in increased IP-10 expression. Inhibition of adenovirus penetration with bafilomycin A1 or ammonium chloride attenuated the activation of ERK-p38 and IP-10 mRNA expression following infection, suggesting that endosomal escape was required to trigger these pathways. In vivo, direct inhibition of ERK and p38 signaling pathways inhibited adenovirus vector-induced IP-10 expression in mouse liver 1 h following transduction. These results demonstrate the importance of signaling via ERK and p38 in the early host response to adenovirus vectors and will permit the development of novel strategies to improve the safety and efficacy of these agents in human gene therapy.


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