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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 expression of phospho-IκB and NF-κB protein were detected using western blot.There was a marked decrease in the levels of phospho-IκB and NF-κB in the NPCs co-cultured with BMSCs compared to the NPCs single culture control. The inhibition was attenuated by treatment of the NPCs with a TGF-β1-specific inhibitor, and strengthened by treatment with recombinant TGF-βl protein. (*p < 0.05, compared to NPCs single culture group).
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f3: Effect of TGF-β1 on the expression of phospho-IκB and NF-κB protein were detected using western blot.There was a marked decrease in the levels of phospho-IκB and NF-κB in the NPCs co-cultured with BMSCs compared to the NPCs single culture control. The inhibition was attenuated by treatment of the NPCs with a TGF-β1-specific inhibitor, and strengthened by treatment with recombinant TGF-βl protein. (*p < 0.05, compared to NPCs single culture group).

Mentions: Up-regulated TGF-β1 from BMSCs improved NPCs degradation significantly. In light of these data, we wondered how TGF-β1 is involved in. Therefore, we next analyzed whether the increase of TGF-β1 affects NF-κB pathway. The levels of phospho-IκB and NF-κB were measured by western blot analysis. There was a marked decrease in the levels of phospho-IκB and NF-κB in the NPCs co-cultured with BMSCs compared to the levels in the NPCs single culture control (p < 0.05). These findings indicate that NF-κB activation and IκB phosphorylation was suppressed in the co-cultured NPCs. Furthermore, the inhibition of NF-κB activation and IκB phosphorylation was attenuated by treatment of the NPCs with SB431542, and strengthened by treatment with recombinant TGF-βl protein (p < 0.05). (Fig. 3).


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 expression of phospho-IκB and NF-κB protein were detected using western blot.There was a marked decrease in the levels of phospho-IκB and NF-κB in the NPCs co-cultured with BMSCs compared to the NPCs single culture control. The inhibition was attenuated by treatment of the NPCs with a TGF-β1-specific inhibitor, and strengthened by treatment with recombinant TGF-βl protein. (*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

f3: Effect of TGF-β1 on the expression of phospho-IκB and NF-κB protein were detected using western blot.There was a marked decrease in the levels of phospho-IκB and NF-κB in the NPCs co-cultured with BMSCs compared to the NPCs single culture control. The inhibition was attenuated by treatment of the NPCs with a TGF-β1-specific inhibitor, and strengthened by treatment with recombinant TGF-βl protein. (*p < 0.05, compared to NPCs single culture group).
Mentions: Up-regulated TGF-β1 from BMSCs improved NPCs degradation significantly. In light of these data, we wondered how TGF-β1 is involved in. Therefore, we next analyzed whether the increase of TGF-β1 affects NF-κB pathway. The levels of phospho-IκB and NF-κB were measured by western blot analysis. There was a marked decrease in the levels of phospho-IκB and NF-κB in the NPCs co-cultured with BMSCs compared to the levels in the NPCs single culture control (p < 0.05). These findings indicate that NF-κB activation and IκB phosphorylation was suppressed in the co-cultured NPCs. Furthermore, the inhibition of NF-κB activation and IκB phosphorylation was attenuated by treatment of the NPCs with SB431542, and strengthened by treatment with recombinant TGF-βl protein (p < 0.05). (Fig. 3).

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