Biomedical Engineering Reference
In-Depth Information
2. Three rate equations describing changes of osteocytes, NO, and
PGE
2
are incorporated in this model.
3. The effect of loading frequency on bone mechanosensitivity is
investigated.
4. The influence of the number of loading cycles during a loading day
and the recovery of bone mechanosensitivity between two loading
bouts as well as during the whole loading period are explored.
5. The Hill equation is extended to two ligands binding to the same cell.
6. A standard BFE is defined to measure the comprehensive bio-
mechanical benefit for bone after remodeling under mechanical
loading.
The use of this model for quantitative analysis has already provided an
insight into the effects of mechanical loading on cortical bone remodeling
[1,2]. This understanding is useful for the development of effective nonphar-
macological therapies to combat bone-related pathologies. In the field of
bone tissue engineering, this improved understanding of how mechanical
conditions affect the formation of bone components by cells at a local level is
essential for the generation of functionally appropriate tissues.
7.2 Development of Mathematical Formulation
7.2.1 RANK-RANKL-OPG Signaling Pathway
The assumption that a coupling mechanism must exist between bone
formation and resorption was first articulated in 1964 [25]. However, the
exact molecular mechanism that describes the interaction between cells
of the osteoblastic and osteoclastic lineages was only recently identified
[26]. Recent breakthroughs in our understanding of osteoclast differentia-
tion and activation have come from the analysis of a family of biologically
related TNF receptor (TNFR)/TNF-like proteins: OPG, the receptor activa-
tor of nuclear factor (NF)-κβ (RANK), and RANK ligand (RANKL), which
together regulate osteoclast function [6,27].
With the discovery of the RANK-RANKL-OPG system, a revolution-
ary understanding of osteoclastogenesis was born. In general, the pathway
involves three major components: (1) the receptor activator of nuclear factor
κ-β (NF-κ-β) (RANK) is expressed on the surface of hemopoietic precursor
cells (here referred to as osteoclast precursor cells); (2) RANKL, a polypep-
tide found on the surface of osteoblastic cells and proteolytically released as
a soluble form; and (3) OPG, a “decoy receptor” molecule released by osteo-
blastic cells [4].
