title: The role of TGF-β1/Smad2/3 pathway in platelet-rich plasma in retarding intervertebral disc degeneration.
abstract: Recent studies have suggested that platelet-rich plasma (PRP) injections are an effective way to retard intervertebral disc degeneration, but the mechanism of action is unclear. Activated platelets release some growth factors, such as transforming growth factor-β1 (TGF-β1), which positively modulate the extracellular matrix of nucleus pulposus cells. The purpose of this study was to explore the mechanism underlying the PRP-mediated inhibition of intervertebral disc degeneration. In an in vitro study, we found that the proliferation of nucleus pulposus cells was greatly enhanced with 2.5% PRP treatment. The TGF-β1 concentration was much higher after PRP treatment. PRP administration effectively increased the collagen II, aggrecan and sox-9 mRNA levels and decreased collagen X levels. However, Western blotting demonstrated that specifically inhibiting TGF-β1 signalling could significantly prevent nucleus pulpous cellular expression of Smad2/3 and matrix protein. In a rabbit study, magnetic resonance imaging revealed significant recovery signal intensity in the intervertebral discs of the PRP injection group compared with the very low signal intensity in the control groups. Histologically, the PRP plus inhibitor injection group had significantly lower expression levels of Smad2/3 and collagen II than the PRP group. These results demonstrated that a high TGF-β1 content in the platelets retarded disc degeneration in vitro and in vivo. Inhibiting the TGF-β1/Smad2/3 pathway could prevent this recovery by inactivating Smad2/3 and down-regulating the extracellular matrix. Therefore, the TGF-β1/Smad2/3 pathway might play a critical role in the ability of PRP to retard intervertebral disc degeneration.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Chunshen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Jiale
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D024043:Collagen Type II / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D000070614:Nucleus Pulposus / Q000473:pathology; D010976:Platelet Count; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1
keywords: TGF-β1/Smad2/3; intervertebral disc degeneration; nucleus pulpous; platelet-rich plasma; rabbit