The Effect of Interleukin 1-β, Platelet Derived Growth Factor-BB and Transforming Growth Factor-β on the expression of PDLs17 mRNA in the Cultured Human Periodontal Ligament Fibroblasts

Apoptotic hepatocytes release factors that activate hepatic stellate cells (HSCs), thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride, or thioacetamide. Histology of hepatotoxicant-induced diseased hepatic tissue correlated with differential expression of fibrosis-related genes. A marked increase in co-staining of transforming growth factor β receptor type II (TGFRIIβ) – desmin or α-smooth muscle actin – platelet-derived growth factor receptor β (PDGFRβ), markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V – cytokeratin expressing hepatocytes. To understand the molecular mechanisms of disease pathology, in vitro experiments were designed using the conditioned medium (CM) of hepatotoxicant-treated HepG2 cells supplemented to HSCs. A significant increase in HSC proliferation, migration, and expression of fibrosis-related genes and protein was observed, thereby suggesting the characteristics of an activated phenotype. Treating HepG2 cells with hepatotoxicants resulted in a significant increase in mRNA expression of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ). CM supplemented to HSCs resulted in increased phosphorylation of PDGFRβ and TGFRIIβ along with its downstream effectors, extracellular signal-related kinase 1/2 and focal adhesion kinase. Neutralizing antibodies against PDGF-BB and TGFβ effectively perturbed the hepatotoxicant-treated HepG2 cell CM-induced activation of HSCs. This study suggests PDGF-BB and TGFβ as potential molecular targets for developing anti-fibrotic therapeutics.

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The Concentration of Plasma Provides Additional Bioactive Proteins in Platelet and Autologous Protein Solutions

The American Journal of Sports Medicine ◽

10.1177/0363546519849671 ◽

2019 ◽

Vol 47 (8) ◽

pp. 1955-1963 ◽

Cited By ~ 1

Author(s):

Sean M. Muir ◽

Natalie Reisbig ◽

Michael Baria ◽

Christopher Kaeding ◽

Alicia L. Bertone

Keyword(s):

Growth Factor ◽

Receptor Antagonist ◽

Laboratory Study ◽

Whole Blood ◽

Transforming Growth Factor ◽

Interleukin 1 ◽

Waste Product ◽

Transforming Growth Factor Β ◽

Interleukin 1 Receptor Antagonist ◽

Unique Source

Background: Currently, platelet-poor plasma (PPP) is a discarded waste product of platelet-rich plasma (PRP) and may contain valuable proteins. Purpose/Hypothesis: The study’s goal was to evaluate the concentration of plasma as a potential additive biotherapy for the treatment of osteoarthritis. We hypothesized that a novel polyacrylamide concentration device would efficiently concentrate insulin-like growth factor–1 (IGF-1) from PPP and be additive to PRP or autologous protein solution (APS). Study Design: Descriptive laboratory study. Methods: A laboratory study was conducted with human and equine whole blood from healthy volunteers/donors. Fresh samples of blood and plasma were processed and characterized for platelet, white blood cell, and growth factor/cytokine content and then quantified by enzyme-linked immunosorbent assays specific for IGF-1, transforming growth factor–β, interleukin-1β, and interleukin-1 receptor antagonist as representatives of cartilage anabolic and inflammatory mediators. Results: A potent cartilage anabolic protein, IGF-1, was significantly concentrated by the polyacrylamide concentration device in both human and equine PPP. The polyacrylamide device also substantially increased plasma proteins over whole blood, most dramatically key proteins relevant to the treatment of osteoarthritis, including transforming growth factor–β (29-fold over blood) and interleukin-1 receptor antagonist (70-fold over plasma). Conclusion: Concentrated PPP is a unique source for biologically relevant concentrations of IGF-1. PRP and APS can produce greater concentrations of other anabolic and anti-inflammatory proteins not found in plasma. Clinical Relevance: The polyacrylamide device efficiently concentrated PPP to create a unique source of IGF-1 that may supplement orthopaedic biologic therapies.

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