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Titolo:
Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts
Autore:
Yudoh, K; Matsuno, H; Nakazawa, F; Katayama, R; Kimura, T;
Indirizzi:
Toyama Med & Pharmaceut Univ, Dept Orthoped Surg, Toyama 9300194, Japan Toyama Med & Pharmaceut Univ Toyama Japan 9300194 Toyama 9300194, Japan
Titolo Testata:
JOURNAL OF BONE AND MINERAL RESEARCH
fascicolo: 8, volume: 16, anno: 2001,
pagine: 1453 - 1464
SICI:
0884-0431(200108)16:8<1453:RTAUTT>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
NORMAL HUMAN-CELLS; HUMAN FIBROBLASTS; LIFE-SPAN; IMMORTAL CELLS; BONE-FORMATION; IN-VITRO; CHROMOSOME INSTABILITY; MAMMALIAN TELOMERASE; PARATHYROID-HORMONE; EPITHELIAL-CELLS;
Keywords:
replicative senescence; osteoporosis; telomerase reverse transcriptase; population doubling osteoblast;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Yudoh, K Toyama Med & Pharmaceut Univ, Dept Orthoped Surg, 2630 Suigtani, Toyama 9300194, Japan Toyama Med & Pharmaceut Univ 2630 Suigtani Toyama Japan 9300194
Citazione:
K. Yudoh et al., "Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts", J BONE MIN, 16(8), 2001, pp. 1453-1464

Abstract

The rate of bone formation is largely determined by the number of osteoblasts, which in turn is determined by the rate of replication of progenitors and the life span of mature cells, reflecting the timing of death by apoptosis. However, the exact age-dependent changes of the cellular activity, replicative potential, and life span of osteoblasts have not been investigatedto date. Here, we present evidence that the cellular activity, telomere lengths, and replicative life span of osteoblastic cells obtained from juxta-articular bone marrow gradually decrease with the advance of donor age. Recently, telomerase reverse transcriptase (hTERT) has been identified as a human telomerase catalytic subunit. We transfected the gene encoding hTERT into telomerase-negative human osteoblastic cells from donors and osteoblastic cell strain NHOst 54881 cells and showed that expression of hTERT inducestelomerase activity in these osteoblastic cells. In contrast to telomerase-negative control cells, which exhibited telomere shortening and senescenceafter 10-15 population doublings, telomerase-expressing osteoblastic cells, had elongated telomere lengths and showed continued alkaline phosphatase activity and procollagen I C-terminal propeptide (PICP) secretion for more than 30 population doublings. These results indicate that osteoblasts; withforced expression of hTERT may be used in cell-based therapies such as ex vivo gene therapy, tissue engineering, and transplantation of osteoblasts to correct bone loss or osteopenia in age-related osteoporotic diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 03:26:07