scholarly journals The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

Cartilage ◽  
2021 ◽  
pp. 194760352110476
Author(s):  
Yannick Nossin ◽  
Eric Farrell ◽  
Wendy J.L.M. Koevoet ◽  
Frank Datema ◽  
Rodrigo A. Somoza ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Nasal Septum ◽  
Healthy Adult ◽  
Cartilage Explants ◽  
Cartilage Tissue ◽  
Human Articular Cartilage ◽  
Cam Assay ◽  
Related Factors

Objective Cartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of complete cartilage releasate with functional assays in vitro and in vivo. Design We evaluated the gene expression profile of angiogenesis-related factors in healthy adult human articular cartilage with a transcriptome-wide analysis generated by next-generation RNAseq. The effect on angiogenesis of the releasate of cartilage tissue was assessed with a chick chorioallantoic membrane (CAM) assay as well as human umbilical vein endothelial cell (HUVEC) migration and proliferation assays using conditioned media generated from tissue-engineered cartilage derived from human articular and nasal septum chondrocytes as well as explants from bovine articular cartilage and human nasal septum. Experiments were done with triplicate samples of cartilage from 3 different donors. Results RNAseq data of 3 healthy human articular cartilage donors revealed that the majority of known angiogenesis-related factors expressed in healthy adult articular cartilage are pro-angiogenic. The releasate from generated cartilage as well as from tissue explants, demonstrated at least a 3.1-fold increase in HUVEC proliferation and migration indicating a pro-angiogenic effect of cartilage. Finally, the CAM assay demonstrated that cartilage explants can indeed attract vessels; however, their ingrowth was not observed. Conclusion Using multiple approaches, we show that cartilage releasate has an inherent pro-angiogenic capacity. It remains vessel free due to anti-invasive properties associated with the tissue itself.

scholarly journals Progenitor Cells Activated by Platelet Lysate in Human Articular Cartilage as a Tool for Future Cartilage Engineering and Reparative Strategies

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1052 ◽  
Author(s):  
Simonetta Carluccio ◽  
Daniela Martinelli ◽  
Maria Elisabetta Federica Palamà ◽  
Rui Cruz Pereira ◽  
Roberto Benelli ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Progenitor Cells ◽  
Articular Chondrocytes ◽  
Ex Vivo ◽  
Primary Cultures ◽  
Platelet Lysate ◽  
Cartilage Explants ◽  
Cartilage Tissue ◽  
Human Articular Cartilage

Regenerative strategies for human articular cartilage are still challenging despite the presence of resident progenitor cell population. Today, many efforts in the field of regenerative medicine focus on the use of platelet derivatives due to their ability to reactivate endogenous mechanisms supporting tissue repair. While their use in orthopedics continues, mechanisms of action and efficacy need further characterization. We describe that the platelet lysate (PL) is able to activate chondro-progenitor cells in a terminally differentiated cartilage tissue. Primary cultures of human articular chondrocytes (ACs) and cartilage explants were set up from donor hip joint biopsies and were treated in vitro with PL. PL recruited a chondro-progenitors (CPCs)-enriched population from ex vivo cartilage culture, that showed high proliferation rate, clonogenicity and nestin expression. CPCs were positive for in vitro tri-lineage differentiation and formed hyaline cartilage-like tissue in vivo without hypertrophic fate. Moreover, the secretory profile of CPCs was analyzed, together with their migratory capabilities. Some CPC-features were also induced in PL-treated ACs compared to fetal bovine serum (FBS)-control ACs. PL treatment of human articular cartilage activates a stem cell niche responsive to injury. These facts can improve the PL therapeutic efficacy in cartilage applications.

Effects of in vitro low oxygen tension preconditioning of buccal fat pad stem cells on in Vivo articular cartilage tissue repair

Life Sciences ◽  
2021 ◽  
pp. 119728
Author(s):  
Fatemeh Dehghani Nazhvani ◽  
Leila Mohammadi Amirabad ◽  
Arezo Azari ◽  
Hamid Namazi ◽  
Simzar Hosseinzadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Tissue Repair ◽  
Cartilage Tissue ◽  
Low Oxygen ◽  
Fat Pad ◽  
Buccal Fat Pad ◽  
Low Oxygen Tension

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.

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 eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

2021 ◽  
Vol 22 (13) ◽  
pp. 6719
Author(s):  
Ashleigh M. Philp ◽  
Sam Butterworth ◽  
Edward T. Davis ◽  
Simon W. Jones
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Cytokines ◽  
Cartilage Damage ◽  
Hip Osteoarthritis ◽  
Matrix Metalloproteases ◽  
Cartilage Explants ◽  
Cartilage Tissue ◽  
Human Articular Cartilage ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Pro Inflammatory Cytokines

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

scholarly journals Effect of different aged cartilage ECM on chondrogenesis of BMSCs in vitro and in vivo

2020 ◽  
Vol 7 (6) ◽  
pp. 583-595
Author(s):  
Xiuyu Wang ◽  
Yan Lu ◽  
Wan Wang ◽  
Qiguang Wang ◽  
Jie Liang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Current Knowledge ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Biological Properties ◽  
Cartilage Tissue ◽  
Before And After ◽  
Marrow Mesenchymal Stem Cells

Abstract Extracellular matrix (ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without exogenous growth factors. The biological properties of ECM scaffolds are primarily depended on the original source, which would directly influence the chondrogenic effects of the ECM materials. Despite the expanding investigations on ECM scaffolds in recent years, the selection of optimized ECM materials in cartilage regeneration was less reported. In this study, we harvested and compared the articular cartilage ECM from newborn, juvenile and adult rabbits. The results demonstrated the significant differences in the mechanical strength, sulphated glycosaminoglycan and collagen contents of the different aged ECM, before and after decellularization. Consequently, different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels, which exerted age-dependent chondrogenic inducibility. In general, both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification. In contrast, BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM. The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification. Together, this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.

scholarly journals Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

2017 ◽  
Vol 114 (10) ◽  
pp. 2556-2561 ◽  
Author(s):  
Johnathan J. Ng ◽  
Yiyong Wei ◽  
Bin Zhou ◽  
Jonathan Bernhard ◽  
Samuel Robinson ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Endochondral Ossification ◽  
Human Articular Cartilage ◽  
Control Groups ◽  
Human Cartilage ◽  
Chondrocyte Maturation ◽  
Self Assembling ◽  
Spatiotemporal Regulation

Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage.

Glycosaminoglycan turn-over in articular cartilage

1975 ◽  
Vol 271 (912) ◽  
pp. 293-313 ◽  
Keyword(s):  
Articular Cartilage ◽  
Femoral Head ◽  
Human Articular Cartilage ◽  
Sulphate Content ◽  
Sulphate Uptake ◽  
Inorganic Sulphate ◽  
The Mean ◽  
Turn Over

Glycosaminoglycan turn-over has been studied both in vivo and in vitro , by using sodium [ 35 S]sulphate as a precursor. The in vivo experiments were performed on rabbits and dogs, taking special care to monitor the 35 S radioactivity in the serum throughout the experiment and to measure the radioactivity due to unincorporated inorganic [ 35 S] sulphate in cartilage at the end of each experiment, in addition to that due to incorporated sulphate. The inorganic sulphate content of the serum was also determined as well as the distribution coefficient for the inorganic sulphate ion between cartilage and serum. From this information it was possible to calculate accurately the rate of sulphate uptake by cartilage in vivo and hence the turn-over rate. Experiments were then performed in vitro on cartilage from rabbits and dogs and the in vivo and in vitro results were compared. A very good agreement was obtained between the two sets of results. Studies were then carried out under exactly the same in vitro conditions on human articular cartilage and it was thus possible to obtain a turn-over rate for the latter which one could trust was close to the actual in vivo value. The mean half-lives thus obtained varied from 45 days for the young rabbit to 150 days for the adult dog and 800 days for the human femoral head. In human cartilage there were considerable variations in turn-over rate within a single joint as a function of depth below the surface, and between different joints. Thus, while the mean half-life for the human femoral head is 800 days, that for the femoral condyle is 300 days. Cartilage from osteoarthrosic femoral heads did not appear to differ much with respect to sulphate uptake from the normal specimens although the turn-over rates were somewhat higher.

scholarly journals Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels

2020 ◽  
Author(s):  
Jacob P. Fredrikson ◽  
Priyanka Brahmachary ◽  
Ebru Erdoğan ◽  
Zach Archambault ◽  
Ronald K. June ◽  
...  
Keyword(s):  
Single Cell ◽  
Dynamic Compression ◽  
Cartilage Tissue Engineering ◽  
Cell Encapsulation ◽  
Cartilage Tissue ◽  
Human Articular Cartilage ◽  
Mechanical Loads ◽  
Single Cell Encapsulation

AbstractHuman articular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened resulting in increased chondrocyte stress. As chondrocytes are responsible for cartilage synthesis and maintenance, it is important to understand how mechanical loads affect cellular responses of chondrocytes. Many studies have examined the chondrocyte response to in vitro mechanical loading by embedding in stiff agarose. However, these experiments are mostly performed in the absence of PCM which may obscure important responses to mechanotransduction. Here, we demonstrate that drop-based microfluidics allows culture of single chondrocytes in alginate microgels for cell-directed PCM synthesis that closely mimics the in vivo microenvironment. Chondrocytes form PCM over 10 days in these single cell microenvironments. Single cell microgels and monolayer controls were encapsulated in high stiffness agarose to mimic the cartilage PCM. After physiological dynamic compression in a custom-built bioreactor, microgels exhibited distinct metabolomic profiles from both uncompressed and monolayer controls. These results demonstrate the potential of single cell encapsulation in alginate microgels to advance cartilage tissue engineering and basic chondrocyte mechanobiology.

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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