P188 Reduces Cell Death and IGF-I Reduces GAG Release Following Single-Impact Loading of Articular Cartilage

2008 ◽  
Vol 130 (4) ◽  
Author(s):  
Roman M. Natoli ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Mechanical Properties ◽  
Cell Death ◽  
Articular Cartilage ◽  
High Impact ◽  
Individual Treatment ◽  
Joint Injury ◽  
Bovine Articular Cartilage ◽  
Treatment Type ◽  
Igf I ◽  
High Level

Prior joint injury predisposes an individual to developing post-traumatic osteoarthritis, for which there is presently no disease modifying treatment. In this condition, articular cartilage degenerates due to cell death and matrix breakdown, resulting in tissue with diminished biomechanical function. P188, a nonionic surfactant, and the growth factor IGF-I have been shown to decrease cell death. Additionally, IGF-I is known to have beneficial effects on cartilage matrix. The objective of this study was to determine the efficacy of P188, IGF-I, and their combination following articular cartilage impact injury with two energy levels, 1.1J (“low”) and 2.8J (“high”), at 24h and 1week. Bovine articular cartilage with attached underlying bone was impacted at the low or high level. Impact sites were explanted and examined immediately, or cultured for 24h or 1week in serum-free media supplemented with P188 (8mg∕ml), IGF-I (100ng∕ml), or their combination. Gross morphology, cell viability, GAG release to the media, and tissue mechanical properties were assessed. Immediately postimpact, high level impacted tissue had significantly increased gross morphology scores, indicating tissue damage, which were maintained over 1week. Gross scores following low impact were initially similar to nonimpacted controls, but, at 24h and 1week, low impact gross scores significantly increased compared to nonimpacted controls. Additionally, at 24h, high impact resulted in increased cell death, and both low and high impacts had increased GAG release compared to nonimpacted controls. Furthermore, high impact caused decreased tissue stiffness at 24h that appeared to worsen over 1week, evident by the percent decrease from nonimpacted controls increasing from 16% to 26%. No treatment type studied mitigated this loss. The combination did not perform better than either individual treatment; however, following low impact at 1week, P188 reduced cell death by 75% compared to no treatment and IGF-I decreased GAG release from the tissue by 49%. In conclusion, high impact resulted in immediate tissue changes that worsened over 1week. Though not causing immediate changes, low impact also resulted in tissue degeneration evident by 24h. No treatment studied was effective at 24h, but by 1week P188 and IGF-I ameliorated established detrimental changes occurring in articular cartilage postimpact. However, further work is needed to optimize treatment strategies to prevent and/or reverse cell death and matrix destruction in a way that maintains tissue mechanical properties, and hence its functionality.

Ameliorating Glycosaminoglycan (GAG) Loss and Cell Death in Articular Cartilage Following Single-Impact Loading

2007 ◽  
Author(s):  
Roman M. Natoli ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Articular Cartilage ◽  
Impact Loading ◽  
Biomechanical Properties ◽  
Cartilage Explants ◽  
Single Impact ◽  
Igf I ◽  
Post Traumatic ◽  
Bioactive Agents

Impact loading of articular cartilage leads to post-traumatic osteoarthritis (OA) through its effects on the cells and extracellular matrix (ECM) of the tissue. Studies have shown the level of impact or injurious compression correlates with increased cell death, degradation of the ECM, and detrimental changes in biomechanical properties [1]. Recently, several bioactive agents, such as P188 and IGF-I, have shown promising results by reducing cell death following injurious compression of cartilage explants [2, 3].

scholarly journals Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes

2015 ◽  
Vol 34 (1) ◽  
pp. 149-153 ◽  
Author(s):  
Darvin J. Griffin ◽  
Kyla F. Ortved ◽  
Alan J. Nixon ◽  
Lawrence J. Bonassar
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Structure Function ◽  
Igf I ◽  
I Gene

scholarly journals Tensile mechanical properties of bovine articular cartilage: Variations with growth and relationships to collagen network components

2003 ◽  
Vol 21 (5) ◽  
pp. 872-880 ◽  
Author(s):  
Amanda K. Williamson ◽  
Albert C. Chen ◽  
Koichi Masuda ◽  
Eugene J.- M. A. Thonar ◽  
Robert L. Sah
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Collagen Network ◽  
Bovine Articular Cartilage

INFLUENCE OF PRE-CONDITIONING LOADS ON BOVINE ARTICULAR CARTILAGE STRESS RELAXATION BEHAVIOR IN CONFINED COMPRESSION

2003 ◽  
Vol 07 (02) ◽  
pp. 145-150
Author(s):  
Diego Correa ◽  
Dennis Cullinane ◽  
Juan Carlos Briceño
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Stress Relaxation ◽  
Solid Phase ◽  
Test Chamber ◽  
Confined Compression ◽  
Equilibrium Stress ◽  
Bovine Articular Cartilage ◽  
Aggregate Modulus ◽  
Compression Chamber

Articular Cartilage is a load bearing tissue whose microarchitecture, electrochemical composition, and fluid interactions afford it unique mechanical properties. It consists of an extracellular matrix (ECM) interspersed with a sparse population of chondrocytes, varying in density by depth. The structure and mechanical properties of this highly specialized tissue also vary depending on depth from the articular surface; with three specialized zones, each with unique material properties. Typically this tissue is mechanically modeled as a biphasic material, consisting of a solid phase and a fluid phase, which can redistribute itself under loading, altering hydrostatic pressure within the material. Thus, articular cartilage exhibits a time-dependent viscoelastic behavior when subjected to constant loading or deformation, and will reach an equilibrium via stress relaxation and creep behavior. The objective of this study was to test a custom designed confined compression chamber. We characterize the ability of the test chamber to generate curves capable of quantifying the stress relaxation level and equilibrium state in bovine articular cartilage, and to show the preliminary results of a comparison between the equilibrium aggregate modulus (HA) obtained from pre- conditioned and non-conditioned tissues. Using fresh bovine articular cartilage samples, stress relaxation tests were conducted in compression, obtaining equilibrium stress and HA through a linear relation between the initial strain and the equilibrium stress. The test specimens were divided into two groups, one with a pre-conditioning load and the other without. The tests resulted in equilibrium stresses of 0.015 ± 0.0067 MPa for the non-conditioned and 0.067 ± 0.012 MPA for the pre-conditioned, and HA values of 0.205 ± 0.100 MPa for the unconditioned group and 0.878 ± 0.160 MPa in the pre-conditioned group. Our confined compression chamber successfully produced the stress relaxation curve characterizing the mechanical behavior of articular cartilage, defining both the equilibrium stress and HA. Our results suggest that pre-conditioning correlates with a higher equilibrium stress and aggregate modulus based on the fact that pre-loading the specimens reduces the effects of viscoelasticity.

Long Term Effect of P188 on Meniscus Preservation Following Blunt Trauma

2012 ◽  
Author(s):  
Adam C. Abraham ◽  
Megan L. Killian ◽  
Roger C. Haut ◽  
Tammy L. Haut Donahue
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Early Stage ◽  
Subsequent Treatment ◽  
Joint Injury ◽  
Secondary Osteoarthritis ◽  
Tissue Degeneration ◽  
Long Term Effect ◽  
Tissue Matrix

Acute knee joint injury has been associated with the development and progression of secondary osteoarthritis (OA). Previous work implicates that acute damage to tissue matrix and cells of the meniscus and articular cartilage may play important roles in early-stage OA [1]. Additionally, it has been shown that articular cartilage matrix repair hinges on chondrocyte preservation [2]. Therefore, inhibition of cell death may halt tissue degeneration. Recently, the FDA-approved surfactant Poloxamer 188 (P-188) has been shown to decrease acute cell death by repair of its plasma membrane, as well as mediate p38 signaling and subsequent inflammatory and apoptotic signaling leading to a reduction in degeneration of impacted cartilage [3, 4]. Therefore, it was hypothesized that matrix glycosaminoglycans of the meniscus will be preserved in the long-term following traumatic impaction and subsequent treatment with P-188.

scholarly journals IGF UPTAKE WITH COMPETITIVE BINDING IN ARTICULAR CARTILAGE

2008 ◽  
Vol 16 (02) ◽  
pp. 175-195 ◽  
Author(s):  
LIHAI ZHANG ◽  
BRUCE S. GARDINER ◽  
DAVID W. SMITH ◽  
PETER PIVONKA ◽  
ALAN J. GRODZINSKY
Keyword(s):  
Articular Cartilage ◽  
Functional Groups ◽  
Dynamic Compression ◽  
Relative Proportion ◽  
Nonlinear Least Squares ◽  
Competitive Binding ◽  
Igf Binding Proteins ◽  
Bovine Articular Cartilage ◽  
Binding Preference ◽  
Igf I

Experiments on the transport of radiolabeled Insulin-like Growth Factors (IGF-I and -II) into bovine articular cartilage show differential uptake depending on the relative proportion of IGF-I and -II. In this study, we present a mathematical model describing both the transport and competition of IGF-I and -II for binding sites represented by two functional groupings of IGF binding proteins (IGFBPs). The first grouping has approximately similar binding affinity to both IGF-I and -II (i.e. IGFBPs 1–5), whereas the second group has significantly higher binding preference for IGF-II compared to IGF-I (i.e. IGFBP-6). Using nonlinear least squares, it is shown that the experimental equilibrium competitive binding results can be described using a reversible Langmuir sorption isotherm involving two dominant IGFBP functional groups.After coupling the sorption model with a poromechanical continuum model, parametric studies are carried out to investigate the effect of model changes including IGF boundary conditions and the ratios of the two IGFBP functional groups. The results show that ignoring competitive binding leads to a significant overestimation of total IGF-I uptake, but an underestimation the rate of "free" (physiologically active) IGF-I within the cartilage. An increase of first group of IGFBPs (i.e. IGFBPs 1–5) as has been reported for osteoarthritis, is observed to hinder the bioavailability of free IGF-I in cartilage, even though the total IGF-I uptake is enhanced. Furthermore, the combination of dynamic compression and competitive binding is seen to enhance the IGF-I uptake within cartilage, but this enhancement is overestimated if competitive binding is neglected.

scholarly journals Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage

1986 ◽  
Vol 240 (2) ◽  
pp. 423-430 ◽  
Author(s):  
D J McQuillan ◽  
C J Handley ◽  
M A Campbell ◽  
S Bolis ◽  
V E Milway ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Calf Serum ◽  
Proteoglycan Synthesis ◽  
Foetal Calf Serum ◽  
Insulin Like Growth Factor ◽  
Bovine Articular Cartilage ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The addition of foetal calf serum to explant cultures of adult bovine articular cartilage is known to stimulate proteoglycan synthesis in a dose-dependent manner. We have now shown the activity in serum responsible for this effect to be heat- and acid-stable, to be associated with a high-Mr complex in normal serum but converted to a low-Mr form under acid conditions. The activity has an apparent Mr approximately 10,000 and isoelectric points similar to those reported for insulin-like growth factors (IGFs). Addition of a monoclonal antibody against insulin-like growth factor-I (IGF-I) prevented foetal calf serum from stimulating proteoglycan synthesis. Physiological concentrations of recombinant IGF-I or pharmacological levels of insulin when added to cartilage cultures mimicked the proteoglycan-stimulatory activity of serum. IGF-I appeared to act by increasing the rate of proteoglycan synthesis and did not change the nature of the proteoglycan synthesized nor the rate of proteoglycan catabolism by the tissue, suggesting that IGF-I may be important in the regulation of proteoglycan metabolism in adult articular cartilage. Furthermore, IGF-I can replace foetal calf serum in the culture medium, thereby allowing the use of a fully-defined medium which will maintain the synthesis and tissue levels of proteoglycan in adult articular cartilage explants for up to 5 days.

scholarly journals Effects of radiopharmaceuticals on articular cartilage’s mechanical properties

Nukleonika ◽  
2019 ◽  
Vol 64 (2) ◽  
pp. 71-74
Author(s):  
Nihal Kuzu ◽  
Ekrem Cicek
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Ionizing Radiation ◽  
Mechanical Tests ◽  
Cartilage Tissue ◽  
Proteoglycan Synthesis ◽  
Bovine Articular Cartilage ◽  
Technetium 99M ◽  
Static Mechanical ◽  
Radiation Science

Abstract As radiation science and technology advances, nuclear medicine applications are increasing worldwide which necessitate the understanding of biological implications of such practices. Ionizing radiation has been shown to cause degraded matrix and reduced proteoglycan synthesis in cartilage, and the late consequences of which may include degenerative arthritis or arthropathy. Although degenerative effects of the ionizing radiation on cartilage tissue have been demonstrated, the effects on the mechanical properties of articular cartilage are largely unknown. The radiopharmaceuticals, technetium-99m and technetium-99m sestamibi, were utilized on bovine articular cartilage to investigate these effects. We used two different mechanical tests to determine the mechanical properties of articular cartilage. Dynamic and static mechanical tests were applied to calculate compressive modulus for articular cartilage. We observed clearly higher control modulus values than that of experimental groups which account for lesser stiffness in the exposed cartilage. In conclusion, compressive moduli of bovine articular cartilage were found to decrease after radiopharmaceutical exposure, after both instantaneous and equilibrium mechanical experiments.

scholarly journals In vitro Articular Cartilage Growth with Sequential Application of IGF-1 and TGF-β1 Enhances Volumetric Growth and Maintains Compressive Properties

2012 ◽  
Vol 134 (3) ◽  
Author(s):  
Nathan T. Balcom ◽  
Britta Berg-Johansen ◽  
Kristin J. Dills ◽  
Jennifer R. Van Donk ◽  
Gregory M. Williams ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Extreme Values ◽  
Volumetric Growth ◽  
Bovine Articular Cartilage ◽  
Poisson's Ratios ◽  
Poisson’S Ratios ◽  
Tgf Β1

In vitro cultures with insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) have previously been shown to differentially modulate the growth of immature bovine articular cartilage. IGF-1 stimulates expansive growth yet decreases compressive moduli and increases compressive Poisson’s ratios, whereas TGF-β1 maintains tissue size, increases compressive moduli, and decreases compressive Poisson’s ratios. The current study’s hypothesis was that sequential application of IGF-1 and TGF-β1 during in vitro culture produces geometric and compressive mechanical properties that lie between extreme values produced when using either growth factor alone. Immature bovine articular cartilage specimens were harvested and either untreated (D0, i.e., day zero) or cultured in vitro for either 6 days with IGF-1 (D6 IGF), 12 days with IGF-1 (D12 IGF), or 6 days with IGF-1 followed by 6 days with TGF-β1 (D12 SEQ, i.e., sequential). Following treatment, all specimens were tested for geometric, biochemical, and compressive mechanical properties. Relative to D0, D12 SEQ treatment enhanced volumetric growth, but to a lower value than that for D12 IGF. Furthermore, D12 SEQ treatment maintained compressive moduli and Poisson’s ratios at values higher and lower, respectively, than those for D12 IGF. Considering the previously described effects of 12 days of treatment with TGF-β1 alone, D12 SEQ induced both growth and mechanical property changes between those produced with either IGF-1 or TGF-β1 alone. The results suggest that it may be possible to vary the durations of select growth factors, including IGF-1 and TGF-β1, to more precisely modulate the geometric, biochemical, and mechanical properties of immature cartilage graft tissue in clinical repair strategies.

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