TGF-βl Suppresses Inflammation in Cell Therapy for Intervertebral Disc Degeneration.
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.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Huilin
H
Yang
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Cheng
C
Cao
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Chunshen
C
Wu
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Chenxi
C
Yuan
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Qiaoli
Q
Gu
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Qing
Q
Shi
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Jun
J
Zou
D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D064987:Cell- and Tissue-Based Therapy; D020219:Chondrogenesis / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007403:Intervertebral Disc / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D053674:Aggrecans; D024043:Collagen Type II; D003470:Culture Media; D020672:I-kappa B Proteins; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D000072000:NF-KappaB Inhibitor alpha