Abstract: Telomere length and telomerase activity are important indicators of cellular senescence and replicative ability. Loss of telomerase is associated with ageing and the development of osteoarthritis. Implantation of telomerase-positive cells, chondrocytes, or stem cells expressing a normal chondrocyte phenotype is desired for cartilage repair procedures. The objective of this study was to identify at what age chondrocytes and at what passage bone marrow-derived mesenchymal stem cells (MSCs) become senescent based on telomerase activity. The effect of osteogenic protein-1 (OP-1) or interleukin-1α (IL-1α) treatment on telomerase activity in chondrocytes was also measured to determine the response to anabolic or catabolic stimuli. Methods: Articular cartilage was collected from horses (n = 12) aged 1 month to 18 years. Chondrocytes from prepubescent horses (<15 months) were treated with OP-1 or IL-1α. Bone marrow aspirate from adult horses was collected and cultured for up to 10 days to isolate MSCs. Telomerase activity was measured using the TeloTAGGG Telomerase PCR ELISA kit. Results: Chondrocytes from prepubescent horses were positive for telomerase activity. Treatment with IL-1α resulted in a decrease in chondrocyte telomerase activity; however, treatment with OP-1 did not change telomerase activity. One MSC culture sample was positive for telomerase activity on day 2; all samples were negative for telomerase activity on day 10. Conclusions: These results suggest that chondrocytes from prepubescent donors are potentially more suitable for cartilage repair procedures and that telomerase activity is diminished by anabolic and catabolic cytokine stimulation. If MSCs are utilized in cartilage repair, minimal passaging should be performed prior to implantation.
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This research explores the relationship between ageing and the activity of telomerase in articular chondrocytes (cells found in the cartilage), and its implications for medical treatments such as cartilage repair. The study found that telomerase activity in these cells decreases after puberty, affects their reparative ability, and that minimally-passaged stem cell therapy might be a successful strategy for cartilage repair.
Objective of the Study
The primary aim of this study was to understand the telomerase activity in chondrocytes and its potential impact on ageing and the development of conditions like osteoarthritis.
This study sought to determine when bone marrow-derived mesenchymal stem cells (MSCs) and chondrocytes become senescent (old and non-functioning) based on telomerase activity.
It also aimed to analyze the effect of certain treatments, such as osteogenic protein-1 (OP-1) and interleukin-1α (IL-1α), on the telomerase activity of chondrocytes.
Research Methods
The researchers collected articular cartilage from horses. The subjects ranged in age from 1 month to 18 years.
Chondrocytes from young horses (less than 15 months old) were treated with OP-1 or IL-1α to study the changes in telomerase activity.
Bone marrow from adult horses was also collected, cultured, and examined up to a period of 10 days to isolate mesenchymal stem cells (MSCs).
The TeloTAGGG Telomerase PCR ELISA kit was used to measure telomerase activity.
Results
Chondrocytes from young (prepubescent) horses showed positive telomerase activity. However, with the treatment of IL-1α, the telomerase activity decreased. OP-1 treatment did not have a significant impact on the telomerase activity of these cells.
Detectable telomerase activity was present in one of the MSC cultures on day 2, but by day 10, all of the MSC samples lacked telomerase activity.
Conclusions
The study concluded that chondrocytes that exhibit telomerase activity are potentially more suitable for cartilage repair procedures. Therefore, cells extracted from prepubescent donors might be more effective for these treatments.
The presence of telomerase activity in MSCs and chondrocytes appears to be affected by both anabolic and catabolic cytokine stimulation. Therefore, if MSCs are to be used in cartilage repair, they should be minimally passaged prior to implantation.
Cite This Article
APA
Wilson B, Novakofski KD, Donocoff RS, Liang YX, Fortier LA.
(2015).
Telomerase Activity in Articular Chondrocytes Is Lost after Puberty.
Cartilage, 5(4), 215-220.
https://doi.org/10.1177/1947603514537518
Department of Clinical Sciences, Cornell University, Ithaca, NY, USA.
Novakofski, Kira D
Department of Clinical Sciences, Cornell University, Ithaca, NY, USA.
Donocoff, Rachel Sacher
Department of Clinical Sciences, Cornell University, Ithaca, NY, USA.
Liang, Yan-Xiang Amber
Department of Clinical Sciences, Cornell University, Ithaca, NY, USA.
Fortier, Lisa A
Department of Clinical Sciences, Cornell University, Ithaca, NY, USA.
Conflict of Interest Statement
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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