Synergistic and Additive Effects of Hydrostatic Pressure and Growth Factor Application on Engineered Articular Cartilage Constructs

2008 ◽  
Author(s):  
Benjamin D. Elder ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Hydrostatic Pressure ◽  
Synergistic Effects ◽  
Biochemical Properties ◽  
Combined Effects ◽  
Additive Effects ◽  
Self Assembled

It has previously been demonstrated that hydrostatic pressure (HP) enhances the biochemical properties of self-assembled articular cartilage constructs [1]. However, studies that systematically assess the effects of HP magnitude and frequency are lacking. Additionally, studies examining the combined effects of hydrostatic pressure and growth factors are limited. To this end, this study sought to test the hypotheses that static HP will have the greatest enhancement of construct biomechanical and biochemical properties, and that there will be additive or synergistic effects when combining growth factors and HP stimulation.

Synergistic and additive effects of drought stress and simulated herbivory on two goldenrods, Solidago altissima and S. gigantea

Botany ◽  
2016 ◽  
Vol 94 (8) ◽  
pp. 635-642 ◽  
Author(s):  
Zoryana Shibel ◽  
Stephen B. Heard
Keyword(s):  
Drought Stress ◽  
Abiotic Stresses ◽  
Synergistic Effects ◽  
Synergistic Action ◽  
Combined Effects ◽  
Additive Effects ◽  
Solidago Altissima ◽  
Simulated Herbivory ◽  
Combined Stresses ◽  
Effects Of Drought

Understanding the combined effects of stressors on plants is important for understanding how they will tolerate herbivory and other damage under unfavorable conditions. When two stresses have synergistic effects, plants may experience particularly strong impacts. We examined individual and combined effects of drought stress and clipping (simulated herbivory) on two species of goldenrods (Solidago altissima L. and S. gigantea Ait.). Each stress reduced production of most plant structures, with drought stress having stronger impacts than clipping. The effects of the two stresses were additive for S. gigantea but synergistic for S. altissima, at least for aboveground biomass and inflorescence biomass. Both species, when under stress, reallocated resources toward asexual reproduction (rhizomes) and away from sexual reproduction (inflorescences). Our results suggest that even closely related plants may tolerate damage differently when under abiotic stresses, and that predicting the additive vs. synergistic action of combined stresses will be difficult.

scholarly journals Serum factors, growth factors and UDP-sugar metabolism in bovine articular cartilage chondrocytes

1994 ◽  
Vol 303 (3) ◽  
pp. 713-721 ◽  
Author(s):  
G E Ysart ◽  
R M Mason
Keyword(s):  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Sugar Metabolism ◽  
Tgf Beta ◽  
Serum Factors ◽  
Bovine Articular Cartilage ◽  
Stimulation Of

1. The effect of different batches of fetal bovine serum and of growth factors on [35S]sulphate incorporation into glycosaminoglycans and on UDP-sugar pools in explant cultures of bovine articular cartilage was investigated. 2. [35S]Sulphate incorporation was variably stimulated between 1.2- and 3.5-fold by four different batches of serum. The UDP-glucuronate pool size expanded 4.3-6.5-fold in the presence of serum, even in those cultures in which little stimulation of [35S]sulphate incorporation occurred. The UDP-N-acetylhexosamine and UDP-hexose pools expanded by about 1.5- and 2.0-fold respectively in the presence of serum. UDP-xylose was not detected. 3. Equilibrium-labelling and pulse-chase experiments with D-[1-3H]glucose indicated that the rate of flux through the UDP-sugar pools was unaffected by serum. UDP-hexose, UDP-N-acetylhexosamine and UDP-glucuronate have approximate half-lives (t1/2) of 7, 12 and 3-4 min respectively. At equilibrium, the 3H specific activities of UDP-hexose and UDP-N-acetylhexosamine were very similar but that for the UDP-glucuronate pool was much higher, especially in serum-supplemented cultures. The results suggest that UDP-glucuronate synthesis occurs via a pathway which is independent of the main UDP-hexose pathway. 4. Supplementing cultures with heat-treated serum had no effect on the serum-induced expansion of UDP-sugar pools but stimulation of [35S]sulphate incorporation into glycosaminoglycans was 50% lower than for native serum. Acid-treated serum promoted a 2-fold expansion of the UDP-glucuronate and UDP-N-acetylhexosamine pool over that obtained with native serum but was 20% less effective in stimulating [35S]sulphate incorporation than the latter. Prior dialysis of serum had no effect on its modulatory action on either [35S]sulphate incorporation or on the size of UDP-sugar pools. 5. Insulin-like growth factor 1 (IGF-1), transforming growth factor beta-1 (TGF beta-1), platelet-derived growth factor (PDGF) (BB homodimer) and epidermal growth factor (EGF) all stimulated [35S]sulphate incorporation into glycosaminoglycans as expected. The UDP-glucuronate pool expanded by 1.5- and 2.0-fold in the presence of IGF-1 and TGF beta-1 respectively, and by about 1.8-fold in the presence of PDGF or EGF. None of the factors investigated, or combinations of IGF-1 and TGF beta-1 or IGF-1 and EGF, stimulated expansion of the UDP-glucuronate pool to the same extent as native serum.(ABSTRACT TRUNCATED AT 400 WORDS)

Growth Factors and Articular Cartilage Rejuvenation: Where are we up to with reversing OA?

2019 ◽  
Author(s):  
Gordon Slater
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Cell Populations ◽  
Disease Modifying ◽  
Stem Cell Populations

Osteoarthritis has eluded a curative/disease modifying treatment despite extensive research over the last century. This is largely due to the extremely slow metabolic turnover of articular cartilage in an essentially avascular environment, along with a pro-catabolic inflammatory cascade that is induced by damage to the healthy cartilage structure. There has been promising data emerging whereby this poor chondrocyte healing process can be improved by applying autologous stem cell populations (harvested from marrow/adipose tissue) that have been programmed to undergo rapid and sustained chondrogenesis with the assistance of numerous chondrogenic growth factors. Here we aim to provide a comprehensive review article about the growth factors employed for the purpose of articular cartilage rejuvenation. Disease modifying agents incorporating chondrogenic growth factors have been extensively researched in the last 2 decades, and it has been identified that the likely chondrogenic growth factor families of most therapeutic value are the Transforming Growth Factor beta (TGF-B superfamily), Fibroblastic Growth Factor (FGF - specifically FGF-18) and Insulin Growth Factor (IGF) in combination with many of the aforementioned factors. There is still a need for consensus on appropriate dosing and long-term studies should be performed to assess the durability of current therapies over many years. The application of growth factor enriched stem cell populations to osteoarthritic cartilage appears to be very near to effective therapeutic use.

scholarly journals Matrix-Bound Growth Factors are Released upon Cartilage Compression by an Aggrecan-Dependent Sodium Flux that is Lost in Osteoarthritis

2021 ◽  
Author(s):  
Stuart J. Keppie ◽  
Jessica C. Mansfield ◽  
Xiaodi Tang ◽  
Christopher J. Philp ◽  
Helen K. Graham ◽  
...  
Keyword(s):  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Tissue Growth ◽  
Acoustic Microscopy ◽  
Matrix Stiffness ◽  
Sodium Flux ◽  
Growth Factor Release ◽  
Factor Release

AbstractArticular cartilage is a dense extracellular matrix-rich tissue that degrades following chronic mechanical stress, resulting in osteoarthritis (OA). The tissue has low intrinsic repair especially in aged and osteoarthritic joints. Here we describe three pro-regenerative factors; fibroblast growth factor 2 (FGF2), connective tissue growth factor, bound to transforming growth factor-beta (CTGF-TGFβ), and hepatoma-derived growth factor (HDGF), that are rapidly released from the pericellular matrix (PCM) of articular cartilage upon mechanical injury. All three growth factors bound heparan sulfate, and were displaced by exogenous NaCl. We hypothesised that sodium, sequestered within the aggrecan-rich matrix, was freed by injurious compression, thereby enhancing the bioavailability of pericellular growth factors. Indeed, growth factor release was abrogated when cartilage aggrecan was depleted by IL-1 treatment, and in severely damaged human osteoarthritic cartilage. A flux in free matrix sodium upon mechanical compression of cartilage was visualised by 23Na magnetic resonance imaging (MRI) just below the articular surface. This corresponded to a region of reduced tissue stiffness, measured by scanning acoustic microscopy and second harmonic generation microscopy, and where Smad2/3 was phosphorylated upon cyclic compression. Our results describe a novel intrinsic repair mechanism, controlled by matrix stiffness and mediated by the free sodium concentration, in which heparan sulfate-bound growth factors are released from cartilage upon injurious load. They identify aggrecan as a depot for sequestered sodium, explaining why osteoarthritic tissue loses its ability to repair. Treatments that restore matrix sodium to allow appropriate release of growth factors upon load are predicted to enable intrinsic cartilage repair in osteoarthritis.Significance StatementOsteoarthritis is the most prevalent musculoskeletal disease, affecting 250 million people worldwide 1. We identify a novel intrinsic repair response in cartilage, mediated by aggrecan-dependent sodium flux, and dependent upon matrix stiffness, which results in the release of a cocktail of pro-regenerative growth factors after injury. Loss of aggrecan in late-stage osteoarthritis prevents growth factor release and likely contributes to disease progression. Treatments that restore matrix sodium in osteoarthritis may recover the intrinsic repair response to improve disease outcome.

scholarly journals Matrix-Bound Growth Factors are Released upon Cartilage Compression by an Aggrecan-Dependent Sodium Flux that is Lost in Osteoarthritis

Function ◽  
2021 ◽  
Author(s):  
Stuart J Keppie ◽  
Jessica C Mansfield ◽  
Xiaodi Tang ◽  
Christopher J Philp ◽  
Helen K Graham ◽  
...  
Keyword(s):  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Tissue Growth ◽  
Acoustic Microscopy ◽  
Matrix Stiffness ◽  
Sodium Flux ◽  
Growth Factor Release ◽  
Factor Release

Abstract Articular cartilage is a dense extracellular matrix-rich tissue that degrades following chronic mechanical stress, resulting in osteoarthritis (OA). The tissue has low intrinsic repair especially in aged and osteoarthritic joints. Here we describe three pro-regenerative factors; fibroblast growth factor 2 (FGF2), connective tissue growth factor, bound to transforming growth factor-beta (CTGF-TGFβ), and hepatoma-derived growth factor (HDGF), that are rapidly released from the pericellular matrix (PCM) of articular cartilage upon mechanical injury. All three growth factors bound heparan sulfate, and were displaced by exogenous NaCl. We hypothesised that sodium, sequestered within the aggrecan-rich matrix, was freed by injurious compression, thereby enhancing the bioavailability of pericellular growth factors. Indeed, growth factor release was abrogated when cartilage aggrecan was depleted by IL-1 treatment, and in severely damaged human osteoarthritic cartilage. A flux in free matrix sodium upon mechanical compression of cartilage was visualised by 23Na magnetic resonance imaging (MRI) just below the articular surface. This corresponded to a region of reduced tissue stiffness, measured by scanning acoustic microscopy and second harmonic generation microscopy, and where Smad2/3 was phosphorylated upon cyclic compression. Our results describe a novel intrinsic repair mechanism, controlled by matrix stiffness and mediated by the free sodium concentration, in which heparan sulfate-bound growth factors are released from cartilage upon injurious load. They identify aggrecan as a depot for sequestered sodium, explaining why osteoarthritic tissue loses its ability to repair. Treatments that restore matrix sodium to allow appropriate release of growth factors upon load are predicted to enable intrinsic cartilage repair in osteoarthritis. Significance Statement Osteoarthritis is the most prevalent musculoskeletal disease, affecting 250 million people worldwide1. We identify a novel intrinsic repair response in cartilage, mediated by aggrecan-dependent sodium flux, and dependent upon matrix stiffness, which results in the release of a cocktail of pro-regenerative growth factors after injury. Loss of aggrecan in late-stage osteoarthritis prevents growth factor release and likely contributes to disease progression. Treatments that restore matrix sodium in osteoarthritis may recover the intrinsic repair response to improve disease outcome.

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