Yudoh K, Matsuno H, Kimura T
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University.
Clin Calcium. 2001 May;11(5):612-8.
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 so far 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 in patients with rheumatoid arthritis or osteoarthritis. Recently, human telomerase reverse transcriptase (hTERT) has been identified as a human teromerase catalytic subunit. We postulate that an expansion of the life-span of osteoblasts and their maintenance as differentiated bone matrix-producing cells may allow for autologus or allogenic cell and gene therapy in bone and joint diseases including osteoporosis. We therefore transfected human osteoblasts with a vector expressing hTERT cDNA, and investigated whether the replicative life-span can be expanded by the introduction of telomerase in human osteoblasts.
骨形成速率在很大程度上由成骨细胞数量决定,而成骨细胞数量又由祖细胞的复制速率和成熟细胞的寿命决定,这反映了通过凋亡导致细胞死亡的时间。然而,迄今为止,尚未对成骨细胞的细胞活性、复制潜能和寿命随年龄的确切变化进行研究。在此,我们提供证据表明,在类风湿性关节炎或骨关节炎患者中,从关节周围骨髓获取的成骨细胞的细胞活性、端粒长度和复制寿命会随着供体年龄的增长而逐渐降低。最近,人类端粒酶逆转录酶(hTERT)已被鉴定为人类端粒酶催化亚基。我们推测,延长成骨细胞的寿命并使其维持为分化的骨基质生成细胞,可能有助于在包括骨质疏松症在内的骨和关节疾病中进行自体或异体细胞及基因治疗。因此,我们用表达hTERT cDNA的载体转染人成骨细胞,并研究引入端粒酶是否能延长人成骨细胞的复制寿命。