Bone Cell Mechanoresponsiveness - Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology - page 176

Fig. 1 Overview of
processes and players in
skeletal mechanotransduction

Mechanical loading

↓

Localized biophysical signal
substrate strain, fluid shear stress

↓

Mechanosensitive bone cells
MSCs, osteoblasts, osteocytes

↓

Biochemical responses and
signaling pathways
Ca 2+ i , ATP, NO, PG, β -catenin

↓

Skeletal adaptation
Osteoblasts and osteoclasts

exception of specialized excitable cells involved in hearing and touch, the cellular
mechanisms responsible for conversion of an external force (e.g., gravity, strain,
hydrostatic pressure, fluid shear stress) into a cellular response generally remain
poorly understood. Burger et al. [ 16 ] described the processes of bone or skeletal
mechanotransduction to involve (Fig. 1 ):

1. Initiation of a cell-level biophysical signal that can be perceived by an

osteocyte;
2. Transduction of this biophysical signal into a biochemical signal;
3. Communication of this biochemical signal to effector cells (osteoblasts or
osteoclasts).

A variety of mechanisms have been proposed that convert an external load into
a pericellular biophysical signal within bone, be it an osteocyte, osteoblast, bone-
lining cell, or mesenchymal stem cell within the bone marrow stroma; such signals
include piezoelectric fields, substrate strain due to deformation of the ECM,
hydrostatic pressure, and, under certain conditions, bone tissue damage (for greater
detail, the reader is directed to the works of Duncan and Turner [ 25 ], Robling et al.
[ 82 ], Turner et al. [ 101 ], or Rubin et al. [ 85 ], amongst many others). Due to its
ability to elicit cellular responses at physiological loading levels in in vitro studies,
the current paradigm is that shear stress due to fluid flow across the body or
dendritic processes of mechanosensory cells is the most likely mechanism
whereby mechanical loading, such as occur during high-impact exercise, elicit
functional skeletal adaptation [ 70 , 107 ]. It should be added that direct substrate
strain, which has been excluded by many investigators due to the absence or