Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Luo, Xuwei; Liu, Kang; Zhu, Chen; Zhao, Ming; Han, Xiaowei; Bai, Yiguang; Feng, Gang

doi:10.1631/jzus.b1500182

Cited by 25 publications

(24 citation statements)

References 38 publications

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“…BMPs are expensive products and limited in use due to short half-lives [64], MSCs could be employed as carriers for BMPs in addition to their proteoglycan production. Possibly, BMP production by transfected MSCs can induce regeneration by resident NP cells and implantation of these genetically modified MSCs might be a very interesting treatment strategy [65][66][67][68][69][70][71].…”

Section: Discussionmentioning

confidence: 99%

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Krouwels

Iljas

Kragten

et al. 2020

IJMS

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Matrix production by nucleus pulposus (NP) cells, the cells residing in the center of the intervertebral disc, can be stimulated by growth factors. Bone morphogenetic proteins (BMPs) hold great promise. Although BMP2 and BMP7 have been used most frequently, other BMPs have also shown potential for NP regeneration. Heterodimers may be more potent than single homodimers, but it is not known whether combinations of homodimers would perform equally well. In this study, we compared BMP2, BMP4, BMP6, and BMP7, their combinations and heterodimers, for regeneration by human NP cells. The BMPs investigated induced variable matrix deposition by NP cells. BMP4 was the most potent, both in the final neotissue glysosaminoglycan content and incorporation efficiency. Heterodimers BMP2/6H and BMP2/7H were more potent than their respective homodimer combinations, but not the BMP4/7H heterodimer. The current results indicate that BMP4 might have a high potential for regeneration of the intervertebral disc. Moreover, the added value of BMP heterodimers over their respective homodimer BMP combinations depends on the BMP combination applied.

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Section: Discussionmentioning

confidence: 99%

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Krouwels

Iljas

Kragten

et al. 2020

IJMS

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“…At present, the transplant of the therapeutic factor gene into nucleus pulposus cells in the lumbar disc has been widely used to increase the composition of various matrices . Cytokines, such as TGF‐β, IGF‐1, CTGF, GDF5, EGF, and BMPs, play an effective role in stimulating the karyomitosis and proteoglycan composition of lumbar disc cells. In degenerated lumbar discs, the content of TGF‐β1 and CTGF decreases, which causes a decrease in proteoglycan and a biomechanical change in lumbar discs .…”

Section: Discussionmentioning

confidence: 99%

The research of transgenic human nucleus pulposus cell transplantation in the treatment of lumbar disc degeneration

Wang

Jin

Kong

et al. 2019

The Kaohsiung J of Med Scie

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The present study determines whether the in vivo injection of TGFβ1 and CTGF mediated by AAV2 to transfect nucleus pulposus cells in degenerative lumbar discs can reverse the biological effects of rhesus lumbar disc degeneration. A total of 42 lumbar discs obtained from six rhesus monkeys were classified into three groups: experimental group, control group, and blank group. Degenerative lumbar discs were respectively injected with double gene-transfected human nucleus pulposus cells using minimally invasive techniques. Immumohistochemical staining, RT-PCR, and western blot were performed to observe the biological effects of double genetransfected human nucleus pulposus cells in degenerative lumbar discs on rhesus lumbar disc degeneration. At 4, 8, and 12 weeks after the transplantation of nucleus pulposus cells, the expression levels of TGF-ß1, CTGF, proteoglycan mRNA, and type-II collagen were detected by RT-PCR. The values of immumohistochemical staining and RT-PCR in the experimental group increased at 8 weeks, decreased with time at 12 weeks, and remained greater than the values in the control group, and the differences were statistically significant (P < .05). The western blot revealed that the values in the experimental group decreased with time, but remained greater than those in the PBS control group and blank control group, and the differences were statistically significant (P < .05). The double gene-transfection of human nucleus pulposus cells in degenerative lumbar discs mediated by rAAV2 can be continuously expressed in vivo after transplantation in lumbar discs of rhesus monkeys, and promotes the synthesis of proteoglycan and type II collagen, achieving the treatment purpose. K E Y W O R D S

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“…It also negatively regulates chondrogenic differentiation through its interaction with noggin (NOG). One study conducted by Luo et al investigated the effects of adenovirus-mediated GDF-5 (AdGDF-5) on ECM expression in human degenerative disc nucleus pulposus (NP) cells in order to determine if AdGDF-5 is a viable therapy to treat intervertebral disc degeneration (IDD) [85]. Like many other studies, they began by determining the expression of GDF-5 in vitro after treating HEK293 cells with AdGDF-5 and then determined the optimal amount of viral vector needed for efficient transduction of NP cells.…”

Section: Using Radv To Treat Cartilage Regenerationmentioning

confidence: 99%

Viruses: Friends and Foes

Rudd¹,

Herrero²

2018

Cartilage Repair and Regeneration

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In this chapter, we will review how viruses can be used to positively affect joints and cartilage of their hosts. Many viruses are arthrogenic, and cause persistent and debilitating arthritis. Even those viruses that are not typically arthrogenic can also cause bone lesions as secondary pathogenesis. Some of these foes include members of the alphaviruses, like chikungunya and Ross River viruses, the rubiviruses, such as rubella, and erythoparvoviruses, like parvovirus B19. Some more uncommon viruses, which can occasionally have detrimental effects on their hosts' joints, include herpes simplex virus, varicella zoster, mumps, human cytomegalovirus, avian orthoreovirus, and caprine arthritis-encephalitis virus. Despite some viruses having negative impacts on cartilage and joints, others have been used as an effective means of gene therapy for bone and cartilage repair. We will take an in-depth look at the current therapeutic strategies for treating arthritis using various viral vectors.

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Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Cited by 25 publications

References 38 publications

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

The research of transgenic human nucleus pulposus cell transplantation in the treatment of lumbar disc degeneration

Viruses: Friends and Foes

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