[Cellular senescence: a mechanism of the development of osteoporosis?].
Osteoporosis is one of the most common diseases of the elderly. This leads to the hypothesis that the ageing of the organism is reflected as a cytogerontological effect in a specific loss of bone cell function. Three underlying pathogenetic mechanisms need to be considered: (1) cellular aging in general, (2) impairment of the systemic stimulation of bone formation by e.g. decreasing hormone levels, and (3) lower cellular effectiveness of cytokines and growth factors. Cellular aging consists of replicative and postmitotic senescence. While the replicative senescence limits only the number of cell cycles, the postmitotic aging is influenced by endo- and exogenous factors. These lead to genetic alterations known as delayed persistent genomic instability and to an increasing impairment of specific cellular functions. In the postmitotic phase, osteopenia caused by the decrease of systemically available sexual hormones is a major field of research. Osteopenia caused by a decreased activity of locally effective cytokines and growth factors is becoming increasingly understood. New therapeutic strategies, which modulate the local osteoblast activity, e.g. in bone defect healing, are under development. In conclusion, cellular senescence is considered to be one element in the development of bone loss. Potential therapeutic targets may open up an additional path in the treatment of local and systemic osteopenias.
Battmann
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Institut für Pathologie, Klinikum der Justus-Liebig-Universität, Langhansstrasse 10, 35385 Giessen. batcave@poboxes.com
Schulz
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A
Stahl
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D000328:Adult; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology* / Q000473:pathology; D002453:Cell Cycle; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D010006:Osteoblasts / Q000166:cytology / Q000473:pathology / Q000502:physiology; D010012:Osteogenesis; D010024:Osteoporosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology* / Q000628:therapy
D016207:Cytokines; D006133:Growth Substances
Zelluläre Seneszenz--ein Mechanismus der Osteoporoseentstehung?