Hyaline Characteristics of Mechanically Induced Cartilaginous Tissues

2007 ◽  
Author(s):  
Kristy T. S. Palomares ◽  
Thomas A. Einhorn ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan
Keyword(s):  
Articular Cartilage ◽  
Mrna Expression ◽  
Mechanical Loading ◽  
Biochemical Composition ◽  
Hyaline Cartilage ◽  
Cartilage Explants ◽  
Tissue Structure ◽  
In Vivo Model ◽  
Extracellular Matrix Components

The mechanical properties of hyaline cartilage depend heavily on tissue structure and biochemical composition. Glycosaminoglycans (GAGs) and collagen fibrils are the key extracellular matrix components of hyaline cartilage that bestow compressive and tensile stiffness, respectively.[1–2] In articular cartilage, a decline in GAG content and collagen organization with injury or with diseases such as osteoarthritis is intimately linked with a decline in mechanical function.[3] In tissue-engineered cartilage and articular cartilage explants, mechanical loading in vitro results in increased aggrecan mRNA expression, GAG content, and increased stiffness.[4–6] These findings suggest that mechanical loading could be applied in vivo to promote cartilage repair via modulation of gene expression, tissue structure, and tissue composition. We have previously developed an in vivo model of skeletal repair in which application of a controlled bending motion to a healing osteotomy gap results in formation of cartilage within the gap.[6] Using this model, we sought to characterize the biochemical composition and collagen structure of the mechanically induced cartilaginous tissue. The objectives of this study were: 1) to quantify the total GAG content and aggrecan mRNA expression; and 2) to characterize the collagen fiber orientation.

MUSCLE-INDUCED PATELLOFEMORAL JOINT LOADING RAPIDLY AFFECTS CARTILAGE mRNA LEVELS IN A SITE SPECIFIC MANNER

2004 ◽  
Vol 08 (01) ◽  
pp. 1-12 ◽  
Author(s):  
Andrea L. Clark ◽  
Linda Mills ◽  
David A Hart ◽  
Walter Herzog
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Patellofemoral Joint ◽  
Mrna Level ◽  
Recovery Period ◽  
Cartilage Explants ◽  
Mrna Levels ◽  
Biological Responses

Mechanical loading of articular cartilage affects the synthesis and degradation of matrix macromolecules. Much of the work in this area has involved mechanical loading of articular cartilage explants or cells in vitro and assessing biological responses at the mRNA and protein levels. In this study, we developed a new experimental technique to load an intact patellofemoral joint in vivo using muscle stimulation. The articular cartilages were cyclically loaded for one hour in a repeatable and measurable manner. Cartilage was harvested from central and peripheral regions of the femoral groove and patella, either immediately after loading or after a three hour recovery period. Total RNA was isolated from the articular cartilage and biological responses were assessed on the mRNA level using the reverse transcriptase-polymerase chain reaction. Articular cartilage from intact patellofemoral joints demonstrated heterogeneity at the mRNA level for six of the genes assessed independent of the loading protocol. Cyclical loading of cartilage in its native environment led to alterations in mRNA levels for a subset of molecules when assessed immediately after the loading period. However, the increases in TIMP-1 and decreases in bFGF mRNA levels were transient; being present immediately after load application but not after a three hour recovery period.

scholarly journals Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1571
Author(s):  
Matilde Tschon ◽  
Francesca Salamanna ◽  
Lucia Martini ◽  
Gianluca Giavaresi ◽  
Luca Lorenzini ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Pain Sensitivity ◽  
Type Ii Collagen ◽  
Male Rats ◽  
In Vivo Model ◽  
Type Ii ◽  
Chemical Induction ◽  
Local Pain ◽  
Gait Parameters

The purpose of this study was to verify the efficacy of a single intra-articular (i.a.) injection of a hyaluronic acid-chitlac (HY-CTL) enriched with two low dosages of triamcinolone acetonide (TA, 2.0 mg/mL and 4.5 mg/mL), in comparison with HY-CTL alone, with a clinical control (TA 40 mg/mL) and with saline solution (NaCl) in an in vivo osteoarthritis (OA) model. Seven days after chemical induction of OA, 80 Sprague Dawley male rats were grouped into five arms (n = 16) and received a single i.a. injection of: 40 mg/mL TA, HY-CTL alone, HY-CTL with 2.0 mg/mL TA (RV2), HY-CTL with 4.5 mg/mL TA (RV4.5) and 0.9% NaCl. Pain sensitivity and Catwalk were performed at baseline and at 7, 14 and 21 days after the i.a. treatments. The histopathology of the joint, meniscus and synovial reaction, type II collagen expression and aggrecan expression were assessed 21 days after treatments. RV4.5 improved the local pain sensitivity in comparison with TA and NaCl. RV4.5 and TA exerted similar beneficial effects in all gait parameters. Histopathological analyses, measured by Osteoarthritis Research Society International (OARSI) and Kumar scores and by immunohistochemistry, evidenced that RV4.5 and TA reduced OA features in the same manner and showed a stronger type II collagen and aggrecan expression; both treatments reduced synovitis, as measured by Krenn score and, at the meniscus level, RV4.5 improved degenerative signs as evaluated by Pauli score. TA or RV4.5 treatments limited the local articular cartilage deterioration in knee OA with an improvement of the physical structure of articular cartilage, gait parameters, the sensitivity to local pain and a reduction of the synovial inflammation.

scholarly journals Mechanical loading regulates expression of talin and its mRNA, which are concentrated at myotendinous junctions

1998 ◽  
Vol 275 (3) ◽  
pp. C818-C825 ◽  
Author(s):  
Jérôme Frenette ◽  
James G. Tidball
Keyword(s):  
Mechanical Loading ◽  
In Vivo Model ◽  
Proteolytic Fragment ◽  
In Vivo Models ◽  
Hindlimb Muscles ◽  
Vitro Model ◽  
Model C ◽  
Myotendinous Junctions

The hypothesis that mechanical loading regulates talin expression in developing and adult muscle was tested using in vitro and in vivo models. Talin was selected for study because it is a key structural link between the cytoskeleton and cell membrane. In the in vitro model, C2C12myotubes were subjected to cyclic strains for 48 h. In the in vivo model, rat hindlimb muscles were unloaded for 10 days, then reloaded for 2 days. Cyclic loading of myotubes resulted in significant increases in the quantity of talin (68%) and its 190-kDa proteolytic fragment (70%), as well as talin mRNA (180%), relative to unloaded myotube cultures. Similarly, talin concentration and its mRNA increased by 68 and 136%, respectively, in soleus muscles reloaded for 2 days relative to ambulatory controls. Immunohistochemistry and in situ RT-PCR showed that talin and its mRNA are concentrated and colocalized at myotendinous junctions. Thus these findings indicate that increased mechanical loading promotes talin synthesis, which occurs principally at myotendinous junctions, according to talin mRNA distribution.

scholarly journals Effect of GCSB-5, a Herbal Formulation, on Monosodium Iodoacetate-Induced Osteoarthritis in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Joon-Ki Kim ◽  
Sang-Won Park ◽  
Jung-Woo Kang ◽  
Yu-Jin Kim ◽  
Sung Youl Lee ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Expression ◽  
Nuclear Factor Κb ◽  
Interleukin 10 ◽  
Cartilage Explants ◽  
Therapeutic Effects ◽  
Monosodium Iodoacetate ◽  
Factor Α

Therapeutic effects of GCSB-5 on osteoarthritis were measured by the amount of glycosaminoglycan in rabbit articular cartilage explantsin vitro, in experimental osteoarthritis induced by intra-articular injection of monoiodoacetate in ratsin vivo. GCSB-5 was orally administered for 28 days.In vitro, GCSB-5 inhibited proteoglycan degradation. GCSB-5 significantly suppressed the histological changes in monoiodoacetate-induced osteoarthritis. Matrix metalloproteinase (MMP) activity, as well as, the levels of serum tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase protein, and mRNA expressions were attenuated by GCSB-5, whereas the level of interleukin-10 was potentiated. By GCSB-5, the level of nuclear factor-κB p65 protein expression was significantly attenuated but, on the other hand, the level of inhibitor of κB-α protein expression was increased. These results indicate that GCSB-5 is a potential therapeutic agent for the protection of articular cartilage against progression of osteoarthritis through inhibition of MMPs activity, inflammatory mediators, and NF-κB activation.

scholarly journals Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine

Development ◽  
2022 ◽  
Author(s):  
Ling Yu ◽  
Yu-Lieh Lin ◽  
Mingquan Yan ◽  
Tao Li ◽  
Emily Y. Wu ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Regenerative Medicine ◽  
Hyaline Cartilage ◽  
Fibroblast Cell ◽  
Similar Response ◽  
Articular Chondrocyte ◽  
Joint Injury ◽  
A Cell ◽  
Culture Strategy

Amputation injuries in mammals are typically non-regenerative, however joint regeneration is stimulated by BMP9 treatment (Yu et al., 2019) indicating the presence of latent articular chondrocyte progenitor cells. BMP9 induces a battery of chondrogenic genes in vivo, and a similar response is observed in cultures of amputation wound cells. Extended cultures of BMP9 treated cells results in differentiation of hyaline cartilage and single cell RNAseq analysis identified wound fibroblasts as BMP9 responsive. This culture model was used to identify a BMP9 responsive adult fibroblast cell line and a culture strategy was developed to engineer hyaline cartilage for engraftment into an acutely damaged joint. Transplanted hyaline cartilage survived engraftment and maintained a hyaline cartilage phenotype but did not form mature articular cartilage. In addition, individual hypertrophic chondrocytes were identified in some samples indicating that the acute joint injury site can promote osteogenic progression of engrafted hyaline cartilage. The findings identify fibroblasts as a cell source for engineering articular cartilage and establishes a novel experimental strategy that bridges the gap between regeneration biology and regenerative medicine.

scholarly journals Hydrogen sulfide promotes calcium uptake in larval zebrafish

2015 ◽  
Vol 309 (1) ◽  
pp. C60-C69 ◽  
Author(s):  
Raymond W. M. Kwong ◽  
Steve F. Perry
Keyword(s):  
Hydrogen Sulfide ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Protein Kinase A ◽  
Whole Body ◽  
In Vivo Model ◽  
Morpholino Knockdown ◽  
Isoform B ◽  
Kinase A

Hydrogen sulfide (H2S) can act as a signaling molecule for various ion channels and/or transporters; however, little is known about its potential involvement in Ca2+ balance. Using developing zebrafish ( Danio rerio) as an in vivo model system, the present study demonstrated that acute exposure to H2S donors increased Ca2+ influx at 4 days postfertilization, while chronic (3-day) exposure caused a rise in whole body Ca2+ levels. The mRNA expression of Ca2+-transport-related genes was unaffected by H2S exposure, suggesting that posttranscriptional modifications were responsible for the altered rates of Ca2+ uptake. Indeed, treatment of fish with the protein kinase A inhibitor H-89 abolished the H2S-mediated stimulation of Ca2+ influx, suggesting that H2S increased Ca2+ influx by activating cAMP-protein kinase A pathways. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are two key enzymes in the endogenous synthesis of H2S. Using an antisense morpholino knockdown approach, we demonstrated that Ca2+ influx was reduced in CBS isoform b (CBSb)- but not in CSE-deficient fish. Interestingly, the reduction in Ca2+ influx in CBSb-deficient fish was observed only in fish that were acclimated to low-Ca2+ water (i.e., 25 μM Ca2+; control: 250 μM Ca2+). Similarly, mRNA expression of cbsb but not cse was increased in fish acclimated to low-Ca2+ water. Results from whole-mount immunohistochemistry further revealed that CBSb was expressed in Na+-K+-ATPase-rich cells, which are implicated in Ca2+ uptake in zebrafish larvae. Collectively, the present study suggests a novel role for H2S in promoting Ca2+ influx, particularly in a low-Ca2+ environment.

scholarly journals 54 A NOVEL AGE- AND STRAIN-DEPENDENT IN VIVO MODEL OF ARTICULAR CARTILAGE HEALING IN MICE

2008 ◽  
Vol 16 ◽  
pp. S38
Author(s):  
N.M. Eltawil ◽  
C. De Bari ◽  
P. Achan ◽  
C. Pitzalis ◽  
F. Dell’Accio
Keyword(s):  
Articular Cartilage ◽  
In Vivo Model ◽  
Cartilage Healing ◽  
Strain Dependent

scholarly journals L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli.

1998 ◽  
Vol 9 (2) ◽  
pp. 203-210 ◽  
Author(s):  
U Haberstroh ◽  
K Stilo ◽  
J Pocock ◽  
G Wolf ◽  
U Helmchen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Northern Blotting ◽  
No Synthase ◽  
In Vivo Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Cell Infiltrate ◽  
Beneficial Effects

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines might play in the regulation of this inflammatory cell infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.

scholarly journals Altered aggrecan synthesis correlates with cell and nucleus structure in statically compressed cartilage

1996 ◽  
Vol 109 (2) ◽  
pp. 499-508 ◽  
Author(s):  
M.D. Buschmann ◽  
E.B. Hunziker ◽  
Y.J. Kim ◽  
A.J. Grodzinsky
Keyword(s):  
Mechanical Loading ◽  
Cellular Response ◽  
Functional Adaptation ◽  
Cartilage Explants ◽  
Spatial Inhomogeneity ◽  
Cartilage Tissue ◽  
Nucleus Structure ◽  
Nucleus Volume

Previous studies have shown that static equilibrium compression of cartilage tissue in vivo and in vitro decreases chondrocyte synthesis of aggrecan molecules. In order to identify mechanisms of cellular response to loading, we have investigated alterations in cell and nucleus structure and the accompanying changes in the synthesis of aggrecan in statically compressed cartilage explants. Using glutaraldehyde fixation and quantitative autoradiography of compressed and radiolabeled cartilage disks we spatially localized newly synthesized aggrecan. Using stereological tools to analyze these same specimens we estimated the cell and nucleus volume, surface area and directional radii. We found that aggrecan synthesis was reduced overall in compressed tissue disks. However, the compression induced a spatial (radial) inhomogeneity in aggrecan synthesis which was not present in uncompressed disks. This spatial inhomogeneity appeared to be directly related to mechanical boundary conditions and the manner in which the load was applied and, therefore, may represent a spatially specific functional adaptation to mechanical loading. Coincident with reduced aggrecan synthesis, we observed reductions in cell and nucleus volume and radii in the direction of compression which were in approximate proportion to the reduction in tissue thickness. Cell and nucleus dimensions perpendicular to the direction of compression did not change significantly. Therefore the observed deformation of the cell and nucleus in statically compressed cartilage approximately followed the dimensional changes imposed on external specimen surfaces. The strong correlation observed between local changes in aggrecan synthesis and alterations in cell and nucleus structure also lend support to certain hypotheses regarding the intracellular signal transduction pathways that may be important in the biosynthetic response of chondrocytes to mechanical loading.

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