Faculty Opinions recommendation of Articular chondrocyte culturing for cell-based cartilage repair: needs and perspectives.

2006 ◽  
Author(s):  
Mats Brittberg
Keyword(s):  
Cartilage Repair ◽  
Articular Chondrocyte

scholarly journals High-Throughput Identification of MiR-145 Targets in Human Articular Chondrocytes

Life ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 58
Author(s):  
Aida Martinez-Sanchez ◽  
Stefano Lazzarano ◽  
Eshita Sharma ◽  
Helen Lockstone ◽  
Christopher L. Murphy
Keyword(s):  
Cartilage Repair ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Articular Chondrocytes ◽  
Articular Chondrocyte ◽  
Coding Region ◽  
Cartilage Development ◽  
Rna Immunoprecipitation ◽  
Important Regulator ◽  
Mmp13 Expression

MicroRNAs (miRNAs) play key roles in cartilage development and homeostasis and are dysregulated in osteoarthritis. MiR-145 modulation induces profound changes in the human articular chondrocyte (HAC) phenotype, partially through direct repression of SOX9. Since miRNAs can simultaneously silence multiple targets, we aimed to identify the whole targetome of miR-145 in HACs, critical if miR-145 is to be considered a target for cartilage repair. We performed RIP-seq (RNA-immunoprecipitation and high-throughput sequencing) of miRISC (miRNA-induced silencing complex) in HACs overexpressing miR-145 to identify miR-145 direct targets and used cWords to assess enrichment of miR-145 seed matches in the identified targets. Further validations were performed by RT-qPCR, Western immunoblot, and luciferase assays. MiR-145 affects the expression of over 350 genes and directly targets more than 50 mRNAs through the 3′UTR or, more commonly, the coding region. MiR-145 targets DUSP6, involved in cartilage organization and development, at the translational level. DUSP6 depletion leads to MMP13 upregulation, suggesting a contribution towards the effect of miR-145 on MMP13 expression. In conclusion, miR-145 directly targets several genes involved in the expression of the extracellular matrix and inflammation in primary chondrocytes. Thus, we propose miR-145 as an important regulator of chondrocyte function and a new target for cartilage repair.

scholarly journals Articular chondrocyte-derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

2020 ◽  
Author(s):  
Ke Ma ◽  
Bo Zhu ◽  
Zetao Wang ◽  
Peian Cai ◽  
Mingwei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Cord ◽  
Cartilage Repair ◽  
Chondrogenic Differentiation ◽  
Phenotypic Expression ◽  
Cartilage Regeneration ◽  
Human Umbilical Cord ◽  
Articular Chondrocyte ◽  
Differentiation And Proliferation

Abstract Background Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that exosomes could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived exosomes (C-EXOs) in chondrogenic differentiation of HUCMSCs has not been reported. Results In this study, we successfully isolated chondrocyte-derived exosomes (C-EXO) from human multi-finger cartilage and found that C-EXO efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A and SOX-9. Also, the expression of the fibrotic marker, COL1A and hypertrophic marker, COL10, was significantly lower than that induced by TGF-β. In vivo, stimulation of C-EXO accelerated HUCMSCs-mediated cartilage repair in rabbit models. Furthermore, C-EXO led to increasing autophagosomes during the process of chondrogenic differentiation, indicating that C-EXO promoted cartilage regeneration might be through the activation of autophagy. Conclusions C-EXOs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

scholarly journals High through-put identification of miR-145 targets in human articular chondrocytes

2020 ◽  
Author(s):  
Aida Martinez-Sanchez ◽  
Stefano Lazzarano ◽  
Eshita Sharma ◽  
Chris L. Murphy
Keyword(s):  
Cartilage Repair ◽  
Motif Discovery ◽  
Articular Chondrocytes ◽  
Biological Processes ◽  
Articular Chondrocyte ◽  
Coding Region ◽  
Rna Immunoprecipitation ◽  
Important Regulator ◽  
Discovery Method ◽  
Mmp13 Expression

ABSTRACTObjectiveMicroRNAs play a key role in biological processes, including cartilage development and homeostasis and are dysregulated in many diseases, including osteoarthritis. MiR-145 modulation induces profound changes in the human articular chondrocyte (HAC) phenotype, partially through direct repression of SOX9. Since miRNAs can simultaneously silence multiple targets, we aimed to identify the whole targetome of miR-145 in HACs. This information is critical if miR-145 is to be considered a target for cartilage repair.MethodsRIP-seq (RNA-immunoprecipitation plus HT-sequencing) of miRISC (miRNA-induced silencing complex) was performed in HACs overexpressing miR-145 to identify miR-145 direct targets. The motif discovery method cWords was used to assess enrichment on miR-145 seed matches in the identified targets. RT-qPCR, Western (immuno-)blot and luciferase assays were used to validate miRNA-target interactions.ResultsMiR-145 overexpression affects the expression of over 350 genes and directly targets more than 50 mRNAs through the 3’UTR or, more commonly, the coding region.We also demonstrate that miR-145 targets DUSP6, involved in cartilage organization and development, at the translational level. DUSP6 depletion using specific siRNAs lead to MMP13 up-regulation, suggesting that miR-145-mediated DUSP6 depletion contributes to the effect of miR-145 on MMP13 expression.ConclusionWe demonstrate that miR-145 directly targets several genes in primary chondrocytes including those involved in the expression of the extracellular matrix and inflammation. Thus, we propose miR-145 as an important regulator of chondrocyte function and a new target for cartilage repair.

scholarly journals HIF-mediated articular chondrocyte function: prospects for cartilage repair

2009 ◽  
Vol 11 (1) ◽  
pp. 213 ◽  
Author(s):  
Christopher L Murphy ◽  
Brendan L Thoms ◽  
Rasilaben J Vaghjiani ◽  
Jérôme E Lafont
Keyword(s):  
Cartilage Repair ◽  
Articular Chondrocyte

scholarly journals Articular chondrocyte derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

2020 ◽  
Author(s):  
Ke Ma ◽  
Bo Zhu ◽  
Zetao Wang ◽  
Peian Cai ◽  
Mingwei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Cartilage Repair ◽  
Chondrogenic Differentiation ◽  
Phenotypic Expression ◽  
Cartilage Regeneration ◽  
Human Umbilical Cord ◽  
Articular Chondrocyte

Abstract Background Umbilical cord mesenchymal stem cells (HUCMSCs)-based therapies were previously predicated in cartilage regeneration due to the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUMSCs is limited by administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported the exosomes could modulate phenotypic expression of stem cells. However, the role of human chondrogenic derived exosomes (C-EXO) in chondrogenic differentiation of HUCMSCs has not been reported. Results In this study, we successfully isolated chondrocyte-derived exosomes (C-EXO) from human multi-finger cartilage and found that C-EXO efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A and SOX-9. Also, the expression of the fibrotic marker, COL1A and hypertrophic marker, COL10, was significantly lower than that induced by TGF-β. In vivo, stimulation of C-EXO accelerated HUCMSCs-mediated cartilage repair in rabbit models. Furthermore, C-EXO led to increasing autophagosomes during the process of chondrogenic differentiation, indicating that C-EXO promoted cartilage regeneration might be through the activation of autophagy. Conclusions This study suggests that C-EXO has an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be a stable supply for articular cartilage repair.

scholarly journals Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Frank A. Petrigliano ◽  
Nancy Q. Liu ◽  
Siyoung Lee ◽  
Jade Tassey ◽  
Arijita Sarkar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Human Embryonic Stem Cell ◽  
Articular Surface ◽  
Embryonic Stem ◽  
Articular Chondrocyte ◽  
Clinical Paradigm ◽  
Financial Burdens

AbstractOsteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.

The role of bone morphogenetic proteins in articular cartilage development, homeostasis and repair

2007 ◽  
Vol 20 (03) ◽  
pp. 151-158 ◽  
Author(s):  
A. O. Oshin ◽  
M. C. Stewart
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Bone Morphogenetic Proteins ◽  
Genetically Engineered ◽  
Articular Chondrocyte ◽  
Diverse Range ◽  
Joint Formation ◽  
Cartilage Development

SummaryBone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of secreted ligands. BMPs regulate a diverse range of developmental processes during embryogenesis and postnatal development, and control the differentiation of several musculoskeletal tissues including bone, cartilage, tendon and ligaments. The ability of BMPs to modulate the phenotype of cells in these tissue lineages suggests that these factors could be valuable for musculoskeletal tissue regeneration. In fact, BMPs-2 and -7 are already in clinical use for bone regeneration. This review addresses the signaling mechanisms by which BMPs regulate cellular processes, the role of BMPs in articular cartilage development and joint formation, and the data that supports the use of BMPs for in vitro phenotypic support of articular chondrocyte cultures, chondrogenic differentiation of mesenchymal stem cells (MSCs) and articular cartilage repair. Given the documented importance of BMP activity for normal joint formation, articular cartilage development and maintenance, the chondrogenic activity of BMPs when applied to MSC cultures and the encouraging outcomes of several in vivo cartilage repair studies, BMP therapies hold considerable promise for effective cartilage repair and/or regeneration. Future advances in the control of BMP elution from biocompatible matrices and prolonged, dose-controlled BMP expression by genetically engineered cells should substantially improve cartilage repair strategies using BMPs and similar chondro-protective proteins.

scholarly journals An In Vitro System to Study the Effect of Subchondral Bone Health on Articular Cartilage Repair in Humans

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1903
Author(s):  
Timothy Hopkins ◽  
Karina T. Wright ◽  
Nicola J. Kuiper ◽  
Sally Roberts ◽  
Paul Jermin ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Subchondral Bone ◽  
Bone Cells ◽  
Cell Types ◽  
Porous Membrane ◽  
Conditioned Media ◽  
Articular Chondrocyte ◽  
Chondrocyte Implantation ◽  
Early Oa

Chondrocyte-based cartilage repair strategies, such as articular chondrocyte implantation, are widely used, but few studies addressed the communication between native subchondral bone cells and the transplanted chondrocytes. An indirect co-culture model was developed, representing a chondrocyte/scaffold-construct repair of a cartilage defect adjoining bone, where the bone could have varying degrees of degeneration. Human BM-MSCs were isolated from two areas of subchondral bone in each of five osteochondral tissue specimens from five patients undergoing knee arthroplasty. These two areas underlaid the macroscopically and histologically best and worst cartilage, representing early and late-stage OA, respectively. BM-MSCs were co-cultured with normal chondrocytes suspended in agarose, with the two cell types separated by a porous membrane. After 0, 7, 14 and 21 days, chondrocyte–agarose scaffolds were assessed by gene expression and biochemical analyses, and the abundance of selected proteins in conditioned media was assessed by ELISA. Co-culture with late-OA BM-MSCs resulted in a reduction in GAG deposition and a decreased expression of genes encoding matrix-specific proteins (COL2A1 and ACAN), compared to culturing with early OA BM-MSCs. The concentration of TGF-β1 was significantly higher in the early OA conditioned media. The results of this study have clinical implications for cartilage repair, suggesting that the health of the subchondral bone may influence the outcomes of chondrocyte-based repair strategies.

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