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TGF-βl Suppresses Inflammation in Cell Therapy for Intervertebral Disc Degeneration.

Yang H, Cao C, Wu C, Yuan C, Gu Q, Shi Q, Zou J - Sci Rep (2015)

Bottom Line: As a strong immune suppressor, TGF-β1 has been shown to inhibit inflammation respond effectively.In vitro assays demonstrated that co-culturing of nucleus pulposus cells with bone marrow mesenchymal stem cells resulted in significantly higher levels of TGF-βl secretion.However, the NF-κB positive cells were significantly less than other two control groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

ABSTRACT
Recent studies suggest that cell therapy may be an effective way to repair intervertebral disc degeneration. As a strong immune suppressor, TGF-β1 has been shown to inhibit inflammation respond effectively. The objective of this study was to explore the effects of TGF-β1 during bone marrow mesenchymal stem cells-based therapy for disc degeneration. In vitro assays demonstrated that co-culturing of nucleus pulposus cells with bone marrow mesenchymal stem cells resulted in significantly higher levels of TGF-βl secretion. This increase inhibited IκB phosphorylation and NF-κB activation, detected by western blot analysis. Meanwhile, in a rabbit model, MRI analysis revealed significant recovery of signal intensity in the degenerative discs of rabbits receiving cells transplantation, than receiving cells treated with a TGF-β1 inhibitor or saline. These findings indicated that enhanced TGF-β1 production recovered the degeneration of intervertebral disc. And also immunohistochemical staining detected enhanced collagen II expression in the rabbits treated with cell transplantation. However, the NF-κB positive cells were significantly less than other two control groups. Thus, cell therapy promoted TGF-β1 expression in nucleus pulposus, leading to anti-inflammatory effects via the inhibition of NF-κB, and the amelioration of disc degradation due to increased expression of collagen II and aggrecan in degenerative intervertebral disc.

No MeSH data available.


Related in: MedlinePlus

Effect of TGF-β1 on the expressions of chondrogenic genes collagen II and aggrecan in vitro.Real-time PCR showed the relative expressions of collagen II and aggrecan were significantly increased in NPCs co-culturing with BMSCs. In contrast, the co-cultured NPCs treated with the TGF-β1 specific inhibitor exhibited stable and low expression levels of mRNA at each time point. (*p < 0.05, compared to NPCs single culture group).
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f2: Effect of TGF-β1 on the expressions of chondrogenic genes collagen II and aggrecan in vitro.Real-time PCR showed the relative expressions of collagen II and aggrecan were significantly increased in NPCs co-culturing with BMSCs. In contrast, the co-cultured NPCs treated with the TGF-β1 specific inhibitor exhibited stable and low expression levels of mRNA at each time point. (*p < 0.05, compared to NPCs single culture group).

Mentions: To find clues to protection of BMSCs against nucleus pulposus degradation, we used real-time PCR to investigate the expression of markers of chondrogenesis. Real-time PCR analyses demonstrated that the mRNA expression levels of the chondrogenic genes collagen II and aggrecan were significantly increased in NPCs after 3 days of co-culturing with BMSCs, compared to the single culture control (p < 0.05). In contrast, no significant differences in expression were observed between the co-culture group and the group treated with recombinant TGF-βl on day 3 (p > 0.05). In contrast, the co-cultured NPCs treated with the TGF-β1 specific inhibitor SB431542 exhibited stable and low expression levels of collagen II and aggrecan mRNA at each time point. No significant differences were observed compared to the NPCs control group at any time point (p > 0.05). (Fig. 2).


TGF-βl Suppresses Inflammation in Cell Therapy for Intervertebral Disc Degeneration.

Yang H, Cao C, Wu C, Yuan C, Gu Q, Shi Q, Zou J - Sci Rep (2015)

Effect of TGF-β1 on the expressions of chondrogenic genes collagen II and aggrecan in vitro.Real-time PCR showed the relative expressions of collagen II and aggrecan were significantly increased in NPCs co-culturing with BMSCs. In contrast, the co-cultured NPCs treated with the TGF-β1 specific inhibitor exhibited stable and low expression levels of mRNA at each time point. (*p < 0.05, compared to NPCs single culture group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542522&req=5

f2: Effect of TGF-β1 on the expressions of chondrogenic genes collagen II and aggrecan in vitro.Real-time PCR showed the relative expressions of collagen II and aggrecan were significantly increased in NPCs co-culturing with BMSCs. In contrast, the co-cultured NPCs treated with the TGF-β1 specific inhibitor exhibited stable and low expression levels of mRNA at each time point. (*p < 0.05, compared to NPCs single culture group).
Mentions: To find clues to protection of BMSCs against nucleus pulposus degradation, we used real-time PCR to investigate the expression of markers of chondrogenesis. Real-time PCR analyses demonstrated that the mRNA expression levels of the chondrogenic genes collagen II and aggrecan were significantly increased in NPCs after 3 days of co-culturing with BMSCs, compared to the single culture control (p < 0.05). In contrast, no significant differences in expression were observed between the co-culture group and the group treated with recombinant TGF-βl on day 3 (p > 0.05). In contrast, the co-cultured NPCs treated with the TGF-β1 specific inhibitor SB431542 exhibited stable and low expression levels of collagen II and aggrecan mRNA at each time point. No significant differences were observed compared to the NPCs control group at any time point (p > 0.05). (Fig. 2).

Bottom Line: As a strong immune suppressor, TGF-β1 has been shown to inhibit inflammation respond effectively.In vitro assays demonstrated that co-culturing of nucleus pulposus cells with bone marrow mesenchymal stem cells resulted in significantly higher levels of TGF-βl secretion.However, the NF-κB positive cells were significantly less than other two control groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

ABSTRACT
Recent studies suggest that cell therapy may be an effective way to repair intervertebral disc degeneration. As a strong immune suppressor, TGF-β1 has been shown to inhibit inflammation respond effectively. The objective of this study was to explore the effects of TGF-β1 during bone marrow mesenchymal stem cells-based therapy for disc degeneration. In vitro assays demonstrated that co-culturing of nucleus pulposus cells with bone marrow mesenchymal stem cells resulted in significantly higher levels of TGF-βl secretion. This increase inhibited IκB phosphorylation and NF-κB activation, detected by western blot analysis. Meanwhile, in a rabbit model, MRI analysis revealed significant recovery of signal intensity in the degenerative discs of rabbits receiving cells transplantation, than receiving cells treated with a TGF-β1 inhibitor or saline. These findings indicated that enhanced TGF-β1 production recovered the degeneration of intervertebral disc. And also immunohistochemical staining detected enhanced collagen II expression in the rabbits treated with cell transplantation. However, the NF-κB positive cells were significantly less than other two control groups. Thus, cell therapy promoted TGF-β1 expression in nucleus pulposus, leading to anti-inflammatory effects via the inhibition of NF-κB, and the amelioration of disc degradation due to increased expression of collagen II and aggrecan in degenerative intervertebral disc.

No MeSH data available.


Related in: MedlinePlus