Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage

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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The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation

Osteoarthritis and Cartilage ◽

10.1016/s1063-4584(96)80009-4 ◽

1996 ◽

Vol 4 (1) ◽

pp. 77-84 ◽

Cited By ~ 107

Author(s):

Jean-Pierre Pelletier ◽

François Mineau ◽

Pierre Ranger ◽

Ginette Tardif ◽

Johanne Martel-Pelletier

Keyword(s):

Nitric Oxide ◽

Articular Chondrocytes ◽

Cartilage Degradation ◽

Human Articular Chondrocytes ◽

Osteoarthritic Cartilage ◽

Inducible Nitric Oxide

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Effects of rAAV-Mediated sox9 Overexpression on the Biological Activities of Human Osteoarthritic Articular Chondrocytes in Their Intrinsic Three-Dimensional Environment

Journal of Clinical Medicine ◽

10.3390/jcm8101637 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1637 ◽

Cited By ~ 1

Author(s):

Oliver Daniels ◽

Janina Frisch ◽

Jagadeesh K. Venkatesan ◽

Ana Rey-Rico ◽

Gertrud Schmitt ◽

...

Keyword(s):

Gene Therapy ◽

Articular Chondrocytes ◽

Biological Activities ◽

Three Dimensional ◽

Type Ii Collagen ◽

Osteoarthritic Cartilage ◽

Cellular Processes ◽

Therapeutic Sequence ◽

Progressive Disorder ◽

Significant Production

Gene therapy for osteoarthritis offers powerful, long-lasting tools that are well adapted to treat such a slow, progressive disorder, especially those therapies based on the clinically adapted recombinant adeno-associated viral (rAAV) vectors. Here, we examined the ability of an rAAV construct carrying a therapeutic sequence for the cartilage-specific SOX9 transcription factor to modulate the phenotype of human osteoarthritic articular chondrocytes compared with normal chondrocytes in a three-dimensional environment where the cells are embedded in their extracellular matrix. Successful sox9 overexpression via rAAV was noted for at least 21 days, leading to the significant production of major matrix components (proteoglycans, type-II collagen) without affecting the proliferation of the cells, while the cells contained premature hypertrophic processes relative to control conditions (reporter rAAV-lacZ application, absence of vector treatment). These findings show the value of using rAAV to adjust the osteoarthritic phenotype when the chondrocytes are confined in their inherently altered environment and the possibility of impacting key cellular processes via gene therapy to remodel human osteoarthritic cartilage lesions.

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Alloreactivity and Immunosuppressive Properties of Articular Chondrocytes from Osteoarthritic Cartilage

Journal of Orthopaedic Surgery ◽

10.1177/1602400222 ◽

2016 ◽

Vol 24 (2) ◽

pp. 232-239 ◽

Cited By ~ 3

Author(s):

Satomi Abe ◽

Hitoshi Nochi ◽

Hiroshi Ito

Keyword(s):

Articular Chondrocytes ◽

Osteoarthritic Cartilage

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α-Catenin Inhibits β-Catenin-T-cell Factor/Lymphoid Enhancing Factor Transcriptional Activity and Collagen Type II Expression in Articular Chondrocytes through Formation of Gli3R·α-Catenin·β-Catenin Ternary Complex

Journal of Biological Chemistry ◽

10.1074/jbc.m111.281014 ◽

2012 ◽

Vol 287 (15) ◽

pp. 11751-11760 ◽

Cited By ~ 8

Author(s):

Jinseol Rhee ◽

Je-Hwang Ryu ◽

Jin-Hong Kim ◽

Churl-Hong Chun ◽

Jang-Soo Chun

Keyword(s):

T Cell ◽

Ternary Complex ◽

Transcriptional Activity ◽

Articular Chondrocytes ◽

Type Ii Collagen ◽

Type Ii ◽

Osteoarthritic Cartilage ◽

T Cell Factor ◽

Collagen Expression ◽

Enhancing Factor

Chondrocytes, a unique cell type in cartilage tissue, are responsible for the regulation of anabolic and catabolic homeostasis in cartilage-specific extracellular matrix synthesis. Activation of Wnt/β-catenin signaling induces dedifferentiation of articular chondrocytes, resulting in suppression of type II collagen expression. We have shown previously that α-catenin inhibits β-catenin-Tcf/Lef (T-cell factor/lymphoid-enhancing factor) transcriptional activity in articular chondrocytes with a concomitant recovery of type II collagen expression. In the current study, we elucidated the mechanism underlying this inhibition of β-catenin-Tcf/Lef transcriptional activity by α-catenin, showing that it requires direct interaction between α-catenin and β-catenin. We further showed that it involves recruitment of Gli3R, the short transcription-repressing form of the transcription factor Gli3, to β-catenin by α-catenin. The resulting inhibition of β-catenin transcriptional activity leads to increased expression of type II collagen. Gli3R and α-catenin actions are co-dependent: both are necessary for the observed inhibitory effects on β-catenin transcriptional activity. Reducing Gli3R expression levels through activation of Indian Hedgehog (Ihh) signaling also is sufficient to activate β-catenin transcriptional activity, suggesting that the ternary complex, Gli3R·α-catenin·β-catenin, mediates Ihh-dependent activation of Wnt/β-catenin signaling in articular chondrocytes. Collectively, this study shows that α-catenin functions as a nuclear factor that recruits the transcriptional repressor Gli3R to β-catenin to inhibit β-catenin transcriptional activity and dedifferentiation of articular chondrocytes. Finally, osteoarthritic cartilage showed elevated levels of β-catenin and decreased levels of α-catenin and Gli3R, suggesting that decreased levels of α-catenin and Gli3R levels contribute to increased β-catenin transcriptional activity during osteoarthritic cartilage destruction.

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