Synergistic effect of combined growth factors in porcine intervertebral disc degeneration

Hongsik Cho, Sang Lee, Sang Hyug Park, Jinsong Huang, Karen Hasty, Song Ja Kim

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Although intervertebral disc (IVD) degeneration is one of most common causes of morbidity, its etiology remains unclear. In healthy discs, the rates of synthesis and breakdown of the extracelluar matrix (ECM) are in equilibrium because of intricate regulation by growth factors and catabolic cytokines. Important among these physiologic growth factors are transforming growth factor-β (TGF-β1) and bone morphogenetic protein-2 (BMP-2). Disc degeneration is thought to be associated with a loss of this homeostasis between proteoglycan (PG) synthesis and cytokine-induced degradation leading to up-regulation of matrix metalloproteinases (MMP) families and down-regulation of extracelluar matrix production. Several strategies using biological agents have been attempted to manage IVD degeneration, improving the function and anabolic capabilities of IVD cells and inhibiting matrix degradation. The purpose of this study is to compare the effects of the anabolic cytokines BMP-2 and TGF-β1 with those of the catabolic cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on porcine annulus fibrosus (AF). The results of this study show that the application of pro-inflammatory cytokines like tumor necrosis factor-α and interleukin-1β to normal annulus fibrosus cells leads to a significant increase in tissue levels of the degradative protease MMP-1. Treatment with a combination of minimum doses of both BMP-2 and TGF-β1 caused a greater decrease in MMP-1 and increase in aggrecan than either cytokine alone, suggesting a synergistic effect of the combined cytokines.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalConnective Tissue Research
Volume54
Issue number3
DOIs
StatePublished - May 13 2013

Fingerprint

Intervertebral Disc Degeneration
Intercellular Signaling Peptides and Proteins
Swine
Cytokines
Bone Morphogenetic Protein 2
Matrix Metalloproteinase 1
Interleukin-1
Tumor Necrosis Factor-alpha
Aggrecans
Degradation
Intervertebral Disc
Biological Factors
Transforming Growth Factors
Proteoglycans
Matrix Metalloproteinases
Homeostasis
Peptide Hydrolases
Up-Regulation
Down-Regulation
Tissue

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Synergistic effect of combined growth factors in porcine intervertebral disc degeneration. / Cho, Hongsik; Lee, Sang; Park, Sang Hyug; Huang, Jinsong; Hasty, Karen; Kim, Song Ja.

In: Connective Tissue Research, Vol. 54, No. 3, 13.05.2013, p. 181-186.

Research output: Contribution to journalArticle

@article{fecc4f74f9e147b1af79866f7384a14f,
title = "Synergistic effect of combined growth factors in porcine intervertebral disc degeneration",
abstract = "Although intervertebral disc (IVD) degeneration is one of most common causes of morbidity, its etiology remains unclear. In healthy discs, the rates of synthesis and breakdown of the extracelluar matrix (ECM) are in equilibrium because of intricate regulation by growth factors and catabolic cytokines. Important among these physiologic growth factors are transforming growth factor-β (TGF-β1) and bone morphogenetic protein-2 (BMP-2). Disc degeneration is thought to be associated with a loss of this homeostasis between proteoglycan (PG) synthesis and cytokine-induced degradation leading to up-regulation of matrix metalloproteinases (MMP) families and down-regulation of extracelluar matrix production. Several strategies using biological agents have been attempted to manage IVD degeneration, improving the function and anabolic capabilities of IVD cells and inhibiting matrix degradation. The purpose of this study is to compare the effects of the anabolic cytokines BMP-2 and TGF-β1 with those of the catabolic cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on porcine annulus fibrosus (AF). The results of this study show that the application of pro-inflammatory cytokines like tumor necrosis factor-α and interleukin-1β to normal annulus fibrosus cells leads to a significant increase in tissue levels of the degradative protease MMP-1. Treatment with a combination of minimum doses of both BMP-2 and TGF-β1 caused a greater decrease in MMP-1 and increase in aggrecan than either cytokine alone, suggesting a synergistic effect of the combined cytokines.",
author = "Hongsik Cho and Sang Lee and Park, {Sang Hyug} and Jinsong Huang and Karen Hasty and Kim, {Song Ja}",
year = "2013",
month = "5",
day = "13",
doi = "10.3109/03008207.2013.775258",
language = "English (US)",
volume = "54",
pages = "181--186",
journal = "Connective Tissue Research",
issn = "0300-8207",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Synergistic effect of combined growth factors in porcine intervertebral disc degeneration

AU - Cho, Hongsik

AU - Lee, Sang

AU - Park, Sang Hyug

AU - Huang, Jinsong

AU - Hasty, Karen

AU - Kim, Song Ja

PY - 2013/5/13

Y1 - 2013/5/13

N2 - Although intervertebral disc (IVD) degeneration is one of most common causes of morbidity, its etiology remains unclear. In healthy discs, the rates of synthesis and breakdown of the extracelluar matrix (ECM) are in equilibrium because of intricate regulation by growth factors and catabolic cytokines. Important among these physiologic growth factors are transforming growth factor-β (TGF-β1) and bone morphogenetic protein-2 (BMP-2). Disc degeneration is thought to be associated with a loss of this homeostasis between proteoglycan (PG) synthesis and cytokine-induced degradation leading to up-regulation of matrix metalloproteinases (MMP) families and down-regulation of extracelluar matrix production. Several strategies using biological agents have been attempted to manage IVD degeneration, improving the function and anabolic capabilities of IVD cells and inhibiting matrix degradation. The purpose of this study is to compare the effects of the anabolic cytokines BMP-2 and TGF-β1 with those of the catabolic cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on porcine annulus fibrosus (AF). The results of this study show that the application of pro-inflammatory cytokines like tumor necrosis factor-α and interleukin-1β to normal annulus fibrosus cells leads to a significant increase in tissue levels of the degradative protease MMP-1. Treatment with a combination of minimum doses of both BMP-2 and TGF-β1 caused a greater decrease in MMP-1 and increase in aggrecan than either cytokine alone, suggesting a synergistic effect of the combined cytokines.

AB - Although intervertebral disc (IVD) degeneration is one of most common causes of morbidity, its etiology remains unclear. In healthy discs, the rates of synthesis and breakdown of the extracelluar matrix (ECM) are in equilibrium because of intricate regulation by growth factors and catabolic cytokines. Important among these physiologic growth factors are transforming growth factor-β (TGF-β1) and bone morphogenetic protein-2 (BMP-2). Disc degeneration is thought to be associated with a loss of this homeostasis between proteoglycan (PG) synthesis and cytokine-induced degradation leading to up-regulation of matrix metalloproteinases (MMP) families and down-regulation of extracelluar matrix production. Several strategies using biological agents have been attempted to manage IVD degeneration, improving the function and anabolic capabilities of IVD cells and inhibiting matrix degradation. The purpose of this study is to compare the effects of the anabolic cytokines BMP-2 and TGF-β1 with those of the catabolic cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on porcine annulus fibrosus (AF). The results of this study show that the application of pro-inflammatory cytokines like tumor necrosis factor-α and interleukin-1β to normal annulus fibrosus cells leads to a significant increase in tissue levels of the degradative protease MMP-1. Treatment with a combination of minimum doses of both BMP-2 and TGF-β1 caused a greater decrease in MMP-1 and increase in aggrecan than either cytokine alone, suggesting a synergistic effect of the combined cytokines.

UR - http://www.scopus.com/inward/record.url?scp=84877255209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877255209&partnerID=8YFLogxK

U2 - 10.3109/03008207.2013.775258

DO - 10.3109/03008207.2013.775258

M3 - Article

VL - 54

SP - 181

EP - 186

JO - Connective Tissue Research

JF - Connective Tissue Research

SN - 0300-8207

IS - 3

ER -