Biomedical Engineering Reference
In-Depth Information
to PTH dosing to discern bone formation responses from bone resorp-
tion. Lemaire et al. [38] incorporated detailed biological information and a
RANK-RANKL-OPG pathway into the remodeling cycle of a model that
included the catabolic effect of PTH on bone, but the anabolic effect of PTH
was not described.
Based on the model of Lemaire et al. [38], Wang, Qin, and Kalyanasundaram
[39] developed a mathematical model that could simulate the anabolic
behavior of bone affected by intermittent administration of PTH; a theo-
retical model and its parametric study of the control mechanisms of bone
remodeling under mechanical stimulus was also developed by Wang and
Qin [40] and Qin and Wang [41]. Pivonka et al. [25,42] extended the bone-
cell population model based on the model of Lemaire et al. [38] to explore
the model structure of cell-cell interactions theoretically [25], and then
they investigated the role of the RANK-RANKL-OPG pathway in bone
remodeling [42].
Although many in vitro and in vivo studies have been performed, the
cellular mechanism by which PEMF affects bone remodeling is still elusive.
To clarify the underlying mechanism at cellular level of regulating the effect
of PEMF on bone remodeling, based on the cell population dynamics model
[25] and the work reported in Wang et al. [39] and Wang and Qin [40], Wang
and Qin [1] developed a mathematical model of bone cell population in bone
remodeling under PEMF using the computational method of system biology.
Wang and Qin [1] used computational system biology to integrate experi-
mental data into a system-level model, enabling the various interactions
to be investigated efficiently and methodically. In particular, the validated
model generated using computational system biology can be used as a tool
to reduce ambiguity as to causes and effects in complex systems such as bone
remodeling, making it possible to test various experimental and theoretical
hypotheses in silico [43], and subsequently to develop pharmaceutical and
clinical interventions for metabolic bone diseases.
8.2 Model Development
8.2.1
Effects of PEMF on Bone Remodeling
The RANK-RANKL-OPG signaling pathway between osteoblasts and osteo-
clasts, PTH, and the dual action of TGF-β is diagrammed in Figure 6.1. PEMF
applies its effects on bone cells partly through this pathway, and this concept
is supported by a number of studies. In an in vitro study [15], a PEMF with a
frequency of 15 Hz (1 G [0.1 mT]; electric field strength 2 mV/cm) was applied
to neonatal mouse calvarial bone cell cultures for 14 days. The results dem-
onstrated that PEMF stimulation significantly increased the proliferation of
