Background and Aim: Telomeres are hexameric repeat sequences that flank eukaryotic chromosomes. The telomere hypothesis of cellular aging proposes that replication of normal somatic cells leads to progressive telomere shortening which induces replicative senescence. Previous studies suggest that growth plate chondrocytes have a finite proliferative capacity in vivo. We therefore hypothesized that telomere shortening in resting zone chondrocytes leads to replicative senescence. Method: To test this hypothesis we compared the telomere restriction fragment (TRF) length of Mus casteneus at 1, 4, 8, and 56 weeks of age. Results and Conclusions: We found that TRF length did not diminish measurably with age, suggesting that telomere shortening in resting zone chondrocytes is not the mechanism that limits proliferation of growth plate chondrocytes in vivo.

1.
Allshire RC, Dempster M, Hastie ND: Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res 1989;17:4611–4627.
2.
Chang JF, Smith CL, Cantor CR: Isolation and characterization of a human telomere. Nucleic Acids Res 1989;17:6109–6127.
3.
Kipling D, Cooke HJ: Hypervariable ultra-long telomeres in mice. Nature 1990;347:400–402.
4.
Schetzlein S, Lucas-Hahn A, Lemme E, Kues WA, Dorsch M, Manns MP, Nieman H, Rudolph KL: Telomere length is reset during early mammalian embryogenesis. Proc Natl Acad Sci USA 2004;101:8034–8038.
5.
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW: Specific association of human telomerase activity with immortal cells and cancer. Science 1994;266:2011–2015.
6.
Shay JW, Bacchetti S: A survey of telomerase activity in human cancer. Eur J Cancer 1997;33:787–791.
7.
Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB: Telomere end-replication problem and cell aging. J Mol Biol 1992;225:951–960.
8.
Rubin H: The disparity between human cell senescence in vitro and lifelong replication in vivo. Nat Biotech 2002;20:675–681.
9.
Cristofalo VJ, Lorenzini A, Allen RG, Torres C, Tresini M: Replicative senescence: A critical review. Mech Ageing Dev 2004;125:827–848.
10.
Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J: The role of resting zone in growth plate chondrogenesis. Endocrinology 2002;143:1851–1857.
11.
Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J: Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci USA 2001;98:6871–6876.
12.
Gafni RI, Weise M, Robrecht DT, Meyers JL, Barnes KM, De-Levi S, Baron J: Catch-up growth is associated with delayed senescence of the growth plate in rabbits. Pediatr Res 2001;50:618–623.
13.
Morita M, Nakanishi K, Kawai T, Fujikawa K: Telomere length, telomerase activity, and expression of human telomerase reverse transcription mRNA in growth plate of epiphyseal articular cartilage in femoral head during normal human development and in thanatophoric dysplasia. Hum Pathol 2004;35:403–411.
14.
Martin JA, Buckwalter JA: Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa Orthop J 2001;21:1–7.
15.
Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu C-P, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE: Extension of life-span by introduction of telomerase into normal human cells. Science 1998;279:349–352.
16.
Harley CB, Futcher AB, Greider CW: Telomeres shorten during aging of human fibroblasts. Nature 1990;345:458–460.
17.
Hathcock KS, Hemann MT, Opperman KK, Strong MA, Greider CW, Hodes RJ: Haploinsufficiency of mTR results in defects in telomere elongation. Proc Natl Acad Sci USA 2002;99:3591–3596.
18.
Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA: Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999;96:701–712.
19.
Hemann MT, Greider CW: Wild-derived inbred mouse strains have short telomeres. Nucleic Acids Res 2000;28:4474–4478.
20.
Kember NF: Cell population kinetics of bone growth: The first ten years of autoradiographic studies with triated thymidine. Clin Orthop 1971;76:213–230.
21.
Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW: Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997;91:25–34.
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