Noble B
Musculo-Skeletal Research Unit, University of Edinburgh Medical School, Edinburgh, Scotland, UK.
Eur Cell Mater. 2003 Dec 21;6:46-55; discusssion 55. doi: 10.22203/ecm.v006a05.
Accumulation of microdamage in bone leads to the reduced strength of our skeleton. In health, bone adapts to the prevailing mechanical needs of the organism and is also capable of self-repair, sensing, removing and replacing damaged or mechanically insufficient volumes of bone. In disease and old age these characteristics are reduced. In order to undertake both of the processes of functional adaptation and repair the bone resorbing and forming cells must be very accurately targeted to areas of physiological need. The mechanism by which cells are precisely targeted to areas requiring repair is both clinically relevant and poorly understood. The osteocyte has been assumed to play a role in sensing damage and signaling for its removal, due largely to its abundance throughout the mineralized bone matrix. However, until recently there has been little evidence that osteocyte function is modified in the vicinity of the microdamage. Here I outline the possibility that the targeted removal of bone containing microcracks might involve signals derived from the apoptotic death of the osteocyte. I shall discuss data that support or refute this view and will consider the possible molecular mechanisms by which controlled cell death might contribute to the signals for repair in the light of work involving cells in bone and other tissue systems.
骨骼中微损伤的积累会导致我们骨骼强度的降低。在健康状态下，骨骼会适应机体当前的机械需求，并且还能够自我修复，感知、清除并替换受损或机械性能不足的骨量。在疾病和老年状态下，这些特性会减弱。为了同时进行功能适应和修复这两个过程，骨吸收细胞和成骨细胞必须非常精确地靶向生理需求区域。细胞精确靶向需要修复区域的机制在临床上具有相关性，但目前了解甚少。由于骨细胞在整个矿化骨基质中含量丰富，因此一直被认为在感知损伤并发出清除损伤信号方面发挥作用。然而，直到最近，几乎没有证据表明微损伤附近的骨细胞功能发生了改变。在此，我概述了一种可能性，即含有微裂纹的骨的靶向清除可能涉及来自骨细胞凋亡死亡的信号。我将讨论支持或反驳这一观点的数据，并将根据涉及骨骼和其他组织系统中细胞的研究，考虑受控细胞死亡可能有助于修复信号的潜在分子机制。
