Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling
Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling
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DOI：
10.1016/s8756-3282(03)00157-1
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发表时间：
2003-08-01
期刊：
影响因子：
4.1
通讯作者：
Wahl, LM
中科院分区：
文献类型：
--
作者：
Komarova, SV;Smith, RJ;Wahl, LM
骨重建在成人骨骼的多个部位异步发生，涉及破骨细胞的再吸收，然后由成骨细胞形成新骨。骨重建的破坏有助于疾病如骨质疏松症、骨关节炎和佩吉特病的发病机制。成骨细胞和破骨细胞之间的相互作用在骨重建的调控中起着至关重要的作用。我们构建了成骨细胞和破骨细胞之间自分泌和旁分泌相互作用的数学模型，使我们能够计算骨重建离散部位的细胞群动力学和骨量变化。该模型预测了不同模式的动态行为：一个单一的重塑周期，响应于外部刺激，一系列的内部调节周期的骨重塑，或不稳定的行为类似于病理性骨重塑佩吉特的疾病。参数分析表明，在系统中的动态行为的模式强烈依赖于破骨细胞的自分泌因子，如转化生长因子P的调节。此外，模拟表明，系统的非线性动力学可以解释不同的影响免疫抑制剂在体外和体内的骨重建。总之，数学模型揭示了成骨细胞和破骨细胞之间的相互作用导致复杂的非线性系统行为，这不能从单独的每种细胞类型的研究中推断出来。该模型将是有用的，在未来的研究中评估细胞因子，生长因子，和潜在的治疗在正常骨和病理条件下，如骨质疏松症和佩吉特病的重塑的整体过程中的影响。(C)2003 Elsevier Science（美国）。All rights reserved.
Bone remodeling occurs asynchronously at multiple sites in the adult skeleton and involves resorption by osteoclasts, followed by formation of new bone by osteoblasts. Disruptions in bone remodeling contribute to the pathogenesis of disorders such as osteoporosis, osteoarthritis, and Paget's disease. Interactions among cells of osteoblast and osteoclast lineages are critical in the regulation of bone remodeling. We constructed a mathematical model of autocrine and paracrine interactions among osteoblasts and osteoclasts that allowed us to calculate cell population dynamics and changes in bone mass at a discrete site of bone remodeling. The model predicted different modes of dynamic behavior: a single remodeling cycle in response to an external stimulus, a series of internally regulated cycles of bone remodeling, or unstable behavior similar to pathological bone remodeling in Paget's disease. Parametric analysis demonstrated that the mode of dynamic behavior in the system depends strongly on the regulation of osteoclasts by autocrine factors, such as transforming growth factor P. Moreover, simulations demonstrated that nonlinear dynamics of the system may explain the differing effects of immunosuppressants on bone remodeling in vitro and in vivo. In conclusion, the mathematical model revealed that interactions among osteoblasts and osteoclasts result in complex, nonlinear system behavior, which cannot be deduced from studies of each cell type alone. The model will be useful in future studies assessing the impact of cytokines, growth factors, and potential therapies on the overall process of remodeling in normal bone and in pathological conditions such as osteoporosis and Paget's disease. (C) 2003 Elsevier Science (USA). All rights reserved.