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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Quantifying osteoblast and osteocyte apoptosis: challenges and rewards.
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Quantifying osteoblast and osteocyte apoptosis: challenges and rewards.

机译：量化成骨细胞和骨细胞凋亡：挑战和回报。

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摘要

Since the initial demonstration of the phenomenon in murine and human bone sections approximately 10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo-long terminal illness in the life of a 75-yr-old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls.
机译：自从大约10年前在鼠和人的骨骼区域首次显示该现象以来，对成骨细胞凋亡的生物学意义的认识不仅极大地有助于理解生理性骨重塑过程中成骨细胞数量的调控，而且还有助于代谢性骨的发病机理疾病和某些用于治疗的药物的药理作用。现已认识到，骨骼代谢的所有主要调节剂包括骨形态发生蛋白（BMP），Wnt，其他生长因子和细胞因子，整联蛋白，雌激素，雄激素，糖皮质激素，PTH和PTH相关蛋白（PTHrP），固定化和氧化性与衰老相关的应激通过调节细胞凋亡来调节成骨细胞和骨细胞的寿命。此外，骨细胞凋亡已成为骨表面重塑的重要调节剂，并且是独立于骨量的骨强度的关键决定因素。由于凋亡仅占成骨细胞寿命的一小部分，因此检测骨切片中的凋亡成骨细胞仍然具有挑战性，这与75岁人类生命中长达6个月的绝症不同。重要的是，这种现象在人类骨活检中不常见50倍，因为人类成骨细胞的寿命更长且数量更少。尽管如此，对细胞凋亡进行良好控制的化验可以准确且可重现地估计该事件的发生率，特别是在有大量成骨细胞供检查的啮齿动物中。从这个角度出发，我们关注该现象的生物学意义，以了解基本的骨骼生物学以及代谢性骨病的发病机理和治疗方法，并讨论量化人体活检中成骨细胞凋亡的现有技术的局限性及其方法学上的缺陷。

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