Telomerase Activity in Articular Chondrocytes Is Lost after Puberty
نویسندگان
چکیده
OBJECTIVE 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.
منابع مشابه
Telomerase activity is lost in articular chondrocytes after puberty
INTRODUCTION Increased age is the most significant predisposing factor for the development of osteoarthritis (OA). As age increases, cells reach replicative senescence, the maximum number of times a somatic cell can divide. It has been suggested in previous studies that replicative scenescence is initiated by telomere erosion, which occurs after the chromosomal telomere falls below a critical l...
متن کاملEffects of telomerase and viral oncogene expression on the in vitro growth of human chondrocytes.
Senescent chondrocytes accumulate with aging in articular cartilage, a process that interferes with cartilage homeostasis and increases the risk of cartilage degeneration. We showed previously that chondrocyte telomere length declines with donor age, which suggests that the aging process is telomere dependent. From these results we hypothesized that telomerase should delay the onset of senescen...
متن کاملComparison between Chondrogenic Markers of Differentiated Chondrocytes from Adipose Derived Stem Cells and Articular Chondrocytes In Vitro
Objective(s): Osteoarthritis is one of the most common diseases in middle-aged population in the world. Cartilage tissue engineering (TE) has been presented as an effort to introduce the best combination of cells, biomaterial scaffolds and stimulating growth factors to produce a cartilage tissue similar to the natural articular cartilage. In this study, the chondrogenic potential of adipose d...
متن کاملCD147 (Extracellular Matrix Metalloproteinase Inducer-EMMPRIN) Expression by Human Articular Chondrocytes
Background: Integrins are a family of transmembrane proteins that allow communication between the extracellular matrix and the interior of cells. Chondrocytes, cells of articular cartilage, express integrins and these molecules appear to have a variety of roles including mechanotransduction. Integrins are known to associate with a number of accessory molecules such as CD147 that may act to regu...
متن کاملHuman telomerase reverse transcriptase (hTERT) extends the lifespan of canine chondrocytes in vitro without inducing neoplastic transformation.
To determine if the exogenous expression of the human telomerase reverse transcriptase (hTERT) protein can extend the in vitro lifespan of chondrocytes from normal and osteoarthritic canine donors, articular chondrocytes were harvested and expanded initially in monolayer culture. Cells were transfected with pCIneo or pCIneo-hTERT and selected using G418. Transfectants were cultured either in mo...
متن کامل