Modeling the interactions between osteoblast and osteoclast activities in bone remodeling
Modeling the interactions between osteoblast and osteoclast activities in bone remodeling
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DOI：
10.1016/j.jtbi.2004.03.023
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发表时间：
2004-08-07
影响因子：
2
通讯作者：
Suva, LJ
中科院分区：
文献类型：
--
作者：
Lemaire, V;Tobin, FL;Suva, LJ
我们提出了一个数学模型来解释成骨细胞和破骨细胞之间的相互作用，这两种细胞类型专门用于维持骨骼的完整性。骨骼是一种动态的、活的组织，其结构和形状在生命过程中不断演变。它有能力通过移除旧骨并在称为重塑的局部过程中用新形成的骨取代来改变结构。这里描述的模型是基于未成熟和成熟成骨细胞的相对比例控制破骨细胞活动程度的思想。此外，破骨细胞根据其分化阶段的不同，对成骨细胞的控制也不同。尽管骨骼调节系统非常复杂，对其了解也很零碎，但我们在模型模拟和从文献中提取的实验观察之间获得了令人惊讶的良好相关性。该模型的结果证实了我们模拟的骨重建系统的所有行为，包括成骨细胞和破骨细胞之间的紧密耦合，持续给予PTH引起的分解代谢作用，RANKL的分解代谢作用，以及可溶性拮抗剂OPG逆转其作用。该模型还能够模拟雌激素缺乏等代谢性骨骼疾病。维生素D缺乏、衰老和糖皮质激素过多。相反，对治疗干预的可能途径进行测试和评估。我们的模型证实，抗吸收疗法不能部分恢复骨丢失，而骨形成疗法产生更好的效果。该模型使我们能够根据疗效确定和评估潜在的治疗方法。特别是，该模型预测，与单一疗法相比，抗吸收疗法和合成代谢疗法的组合提供了显著的好处，特别是对某些类型的骨骼疾病。最后，该模型清楚地表明，增加成骨细胞池的大小是骨形成治疗操作的基本要素。该模型被构思为骨转换建模平台的第一步。这些初步的建模结果非常令人鼓舞，并引导我们继续对骨转换和骨骼重塑进行更多的探索。(C)2004爱思唯尔有限公司。保留所有权利。
We propose a mathematical model explaining the interactions between osteoblasts and osteoclasts, two cell types specialized in the maintenance of the bone integrity. Bone is a dynamic, living tissue whose structure and shape continuously evolves during life. It has the ability to change architecture by removal of old bone and replacement with newly formed bone in a localized process called remodeling. The model described here is based on the idea that the relative proportions of immature and mature osteoblasts control the degree of osteoclastic activity. In addition, osteoclasts control osteoblasts differentially depending on their stage of differentiation. Despite the tremendous complexity of the bone regulatory system and its fragmentary understanding, we obtain surprisingly good correlations between the model simulations and the experimental observations extracted from the literature. The model results corroborate all behaviors of the bone remodeling system that we have simulated, including the tight coupling between osteoblasts and osteoclasts, the catabolic effect induced by continuous administration of PTH, the catabolic action of RANKL, as well as its reversal by soluble antagonist OPG. The model is also able to simulate metabolic bone diseases such as estrogen deficiency. vitamin D deficiency, senescence and glucocorticoid excess. Conversely, possible routes for therapeutic interventions are tested and evaluated. Our model confirms that anti-resorptive therapies are unable to partially restore bone loss, whereas bone formation therapies yield better results. The model enables us to determine and evaluate potential therapies based on their efficacy. In particular, the model predicts that combinations of anti-resorptive and anabolic therapies provide significant benefits compared with monotherapy, especially for certain type of skeletal disease. Finally, the model clearly indicates that increasing the size of the pool of preosteoblasts is an essential ingredient for the therapeutic manipulation of bone formation. This model was conceived as the first step in a bone turnover modeling platform. These initial modeling results are extremely encouraging and lead us to proceed with additional explorations into bone turnover and skeletal remodeling. (C) 2004 Elsevier Ltd. All rights reserved.