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Reconstituting Telomerase Activity Using the Telomerase Catalytic Subunit Prevents the Telomere Shorting and Replicative Senescence in Human Osteoblasts
Author(s) -
Yudoh Kazuo,
Matsuno Hiroaki,
Nakazawa Fujio,
Katayama Rie,
Kimura Tomoatsu
Publication year - 2001
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2001.16.8.1453
Subject(s) - telomerase , telomere , telomerase reverse transcriptase , biology , population , senescence , progenitor cell , microbiology and biotechnology , stem cell , protein subunit , cancer research , genetics , gene , medicine , environmental health
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 investigated to 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 induces telomerase activity in these osteoblastic cells. In contrast to telomerase‐negative control cells, which exhibited telomere shortening and senescence after 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 with forced 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.