Li D, Yuan Q, Wang W
Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, China.
J Int Med Res. 2012;40(4):1242-50. doi: 10.1177/147323001204000403.
The telomeric region of repetitive DNA sequences at the end of chromosomes prevents end-to-end fusion of chromosome terminals and deterioration of the doublestrand free ends. Because of the 'end-replication problem', telomeres shorten with each round of cell division, resulting in cell senescence. The enzyme telomerase compensates for telomere shortening by elongating telomeric sequences, thereby prolonging the lifespan of the cell. Studies of articular cartilage and bone tissues have indicated that telomere shortening limits normal cell function and proliferation, while the telomere maintenance mechanisms of osteosarcoma cells facilitate escape from cell death and promote immortality. This article reviews the literature on this topic and provides an extensive discussion of the basic molecular biology and roles of telomeres and telomerase in musculoskeletal diseases such as osteoarthritis, osteoporosis and osteosarcoma. Findings to date suggest that telomeres and telomerase may become novel therapeutic targets for the diagnosis, treatment and prevention of musculoskeletal disorders.
染色体末端的重复DNA序列组成的端粒区域可防止染色体末端发生端端融合以及双链游离端的降解。由于“末端复制问题”，端粒会随着细胞的每一轮分裂而缩短，从而导致细胞衰老。端粒酶通过延长端粒序列来补偿端粒缩短，从而延长细胞寿命。对关节软骨和骨组织的研究表明，端粒缩短会限制正常细胞功能和增殖，而骨肉瘤细胞的端粒维持机制则有助于其逃避细胞死亡并促进永生。本文综述了该主题的文献，并对端粒和端粒酶在骨关节炎、骨质疏松症和骨肉瘤等肌肉骨骼疾病中的基本分子生物学及作用进行了广泛讨论。迄今为止的研究结果表明，端粒和端粒酶可能成为诊断、治疗和预防肌肉骨骼疾病的新型治疗靶点。
