Articular chondrocytes from osteoarthritic knee joints of elderly, in vitro expanded in thermo-reversible gelation polymer (TGP), exhibiting higher UEA-1 expression in lectin microarray

In vitro characterization of human articular chondrocytes and chondroprogenitors derived from normal and osteoarthritic knee joints

10.1101/440107 ◽

2018 ◽

Author(s):

Elizabeth Vinod ◽

Upasana Kachroo ◽

Solomon Sathishkumar ◽

P.R.J.V.C Boopalan

Keyword(s):

Articular Chondrocytes ◽

Knee Joints ◽

Adhesion Assay ◽

Human Articular Cartilage ◽

Cell Type ◽

Biological Profile ◽

Osteoarthritic Cartilage ◽

Osteoarthritic Knee ◽

Cell Based Therapy

AbstractObjectiveCell based therapy optimization is constantly underway since regeneration of genuine hyaline cartilage is under par. Although single source derivation of chondrocytes and chondroprogenitors is advantageous, lack of a characteristic differentiating marker obscures clear identification of either cell type which is essential to create a biological profile and is also required to assess cell type superiority for cartilage repair. This study was the first attempt where characterization was performed on the two cell populations derived from the same human articular cartilage samples.DesignCells obtained from normal/osteoarthritic knee joints were expanded in culture (up to passage 10). Characterization studies was performed using flow cytometry, gene expression was studied using RT-PCR, growth kinetics and tri-lineage differentiation was also studied to construct a better biological profile of chondroprogenitors as well as chondrocytes.Results and conclusionsOur results suggest that sorting based on CD34(-), CD166(+) and CD146(+), instead of isolation using fibronectin adhesion assay (based on CD49e+/CD29+), would yield a population of cells primarily composed of chondroprogenitors which when derived from normal as opposed to osteoarthritic cartilage, could provide translatable results in terms of enhanced chondrogenesis and reduced hypertrophy; both indispensable for the field of cartilage regeneration.

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Effect ofAngelica sinensisPolysaccharides on OsteoarthritisIn VivoandIn Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/794761 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 9

Author(s):

Jun Qin ◽

Yan-song Liu ◽

Jun Liu ◽

Jing Li ◽

Yang Tan ◽

...

Keyword(s):

Mrna Expression ◽

Articular Chondrocytes ◽

Interleukin 1 ◽

Knee Joints ◽

Protective Effects ◽

Interleukin 1 Beta ◽

Degrading Enzymes ◽

Matrix Degrading Enzymes

This study investigated the effect ofAngelica sinensispolysaccharides (APS-3c) on rat osteoarthritis (OA) modelin vivoand rat interleukin-1-beta- (IL-1β-) stimulated chondrocytesin vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilagein vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1β in vitro. 2~50 μg/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1β. Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1βbut did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA modelin vivoand IL-1β-stimulated chondrocytesin vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.

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CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage

International Journal of Molecular Sciences ◽

10.3390/ijms21207556 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7556

Author(s):

Miho Kuwahara ◽

Koichi Kadoya ◽

Sei Kondo ◽

Shanqi Fu ◽

Yoshiko Miyake ◽

...

Keyword(s):

Articular Cartilage ◽

Transgenic Mice ◽

Articular Chondrocytes ◽

Knee Joints ◽

Ccn Family ◽

Human Knee ◽

Protein Levels ◽

Enhanced Expression ◽

P53 Mrna

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.

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Systematic investigation and in vitro biocompatibility studies on implantable magnetic nanocomposites for hyperthermia treatment of osteoarthritic knee joints

Journal of Materials Science ◽

10.1007/s10853-017-1136-0 ◽

2017 ◽

Vol 52 (16) ◽

pp. 9262-9268 ◽

Cited By ~ 4

Author(s):

S. Mohapatra ◽

R. Mishra ◽

P. Roy ◽

K. L. Yadav ◽

S. Satapathi

Keyword(s):

Systematic Investigation ◽

Knee Joints ◽

Magnetic Nanocomposites ◽

Hyperthermia Treatment ◽

Osteoarthritic Knee ◽

In Vitro Biocompatibility

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pNNS-Conjugated Chitosan Mediated IGF-1 and miR-140 Overexpression in Articular Chondrocytes Improves Cartilage Repair

BioMed Research International ◽

10.1155/2019/2761241 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Rong-lan Zhao ◽

Xu-mei Zhang ◽

Li-na Jia ◽

Wei Song ◽

Yan-li Sun ◽

...

Keyword(s):

Articular Chondrocytes ◽

Single Gene ◽

Negative Control ◽

Knee Joints ◽

Cartilage Defects ◽

Kinase Substrate ◽

Biologic Effects ◽

Localization Signal

The aim of the present study was to investigate the effects of phosphorylatable nucleus localization signal linked nucleic kinase substrate short peptide (NNSp)-conjugated chitosan (NNSp-CS) mediated miR-140 and IGF-1 in both rabbit chondrocytes and cartilage defects model. NNSp-CS was combined with pBudCE4.1-IGF-1, pBudCE4.1-miR-140, and negative control pBudCE4.1 to form pDNA/NNSp-CS complexes. Then these complexes were transfected into chondrocytes or injected intra-articularly into the knee joints. High levels of IGF-1 and miR-140 expression were detected both in vitro and in vivo. Compared with pBudCE4.1 group, in vitro, the transgenic groups significantly promoted chondrocyte proliferation, increased glycosaminoglycan (GAG) synthesis, and ACAN, COL2A1, and TIMP-1 levels, and reduced the levels of nitric oxide (NO), MMP-13, and ADAMTS-5. In vivo, the exogenous genes enhanced COL2A1, ACAN, and TIMP-1 expression in cartilage and reduced cartilage Mankin score and the contents of NO, IL-1β, TNF-α, and GAG contents in synovial fluid of rabbits, MMP-13, ADAMTS-5, COL1A2, and COL10A1 levels in cartilage. Double gene combination showed better results than single gene. This study indicate that NNSp-CS is a better gene delivery vehicle in gene therapy for cartilage defects and that miR-140 combination IGF-1 transfection has better biologic effects on cartilage defects.

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Characterization of human articular chondrocytes and chondroprogenitors derived from non-diseased and osteoarthritic knee joints to assess superiority for cell-based therapy

Acta Histochemica ◽

10.1016/j.acthis.2020.151588 ◽

2020 ◽

Vol 122 (6) ◽

pp. 151588

Author(s):

Elizabeth Vinod ◽

Upasana Kachroo ◽

Grace Rebekah ◽

Bijesh Kumar Yadav ◽

Boopalan Ramasamy

Keyword(s):

Articular Chondrocytes ◽

Human Articular Chondrocytes ◽

Knee Joints ◽

Osteoarthritic Knee ◽

Cell Based Therapy

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Faculty Opinions recommendation of A predominant Th1 polarization is present in synovial fluid of end-stage osteoarthritic knee joints: analysis of peripheral blood, synovial fluid and synovial membrane.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734307291.793573705 ◽

2020 ◽

Author(s):

Susanne Grässel

Keyword(s):

Synovial Fluid ◽

Peripheral Blood ◽

Synovial Membrane ◽

Knee Joints ◽

Osteoarthritic Knee ◽

End Stage ◽

Th1 Polarization

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Faculty Opinions recommendation of Transcriptional response of human articular chondrocytes treated with fibronectin fragments: an in vitro model of the osteoarthritis phenotype.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739123584.793581017 ◽

2020 ◽

Author(s):

Peter Torzilli

Keyword(s):

In Vitro Model ◽

Articular Chondrocytes ◽

Transcriptional Response ◽

Human Articular Chondrocytes ◽

Fibronectin Fragments ◽

Vitro Model

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KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats

Scientific Reports ◽

10.1038/s41598-021-95173-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sachiko Iwai ◽

Hanako O. Ikeda ◽

Hisashi Mera ◽

Kohei Nishitani ◽

Motoo Saito ◽

...

Keyword(s):

Cell Death ◽

Er Stress ◽

Apoptotic Cell ◽

Intraperitoneal Administration ◽

Atp Depletion ◽

Knee Joints ◽

Cellular Protection ◽

Monosodium Iodoacetate

AbstractCurrently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA.

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