Page 57 - Physico-Chemical Niche Conditions for Bone Cells

INTRODUCTION
In orthodontics, (oral) implantology, and orthopedics, mechanical stimuli are known to modulate bone mass, strength, and microstructure [1]. Changes in bone induced by orthodontic forces are modulated by the periodontal ligament [2]. However, direct sensing of mechanical loads, or lack thereof, by osteocytes and osteoblasts also plays an important role in the shaping of bone tissue [3–5]. Both osteocytes and osteoblasts are responsive to the loading-induced flow of fluid, albeit osteocytes are most responsive [6]. Since osteoblasts (which terminally differentiate into osteocytes) respond to fluid flow-induced shear stress in vitro, osteoblasts provide a practical model for studying bone cell responses to shear stress. Fluid flow induced by four-point-bending of rat tibiae in vivo has been confirmed by tracer methods [7]. After sensing mechanical signals, osteocytes or osteoblasts translate the mechanical signal into a biological response, through a process known as mechanotransduction.
Mechanotransduction plays a vital role in bone, where it eventually results in an anabolic or catabolic biological reaction. Pathological unloading of bone unequivocally leads to bone loss, while physiological mechanical stimuli decrease bone resorption and promote bone formation in vivo [8]. Further intensification of the mechanical stimulus leads to overloading-induced bone loss. Overloading causes microdamage, osteocyte apoptosis, and stimulation of osteoclast formation and activity, but it may also induce a direct catabolic response in bone cells [9]. It is not yet fully understood which factors determine whether a mechanical stimulus is osteo-anabolic or osteo-catabolic, or even how a physiological mechanical signal is altered into an anabolic chemical response within the cell. More knowledge of the mechanotransduction process would aid oral implantology, orthodontics, and orthopedics by increasing the understanding of the mechanisms driving mechanical loading-induced bone adaptation.
Mechanotransduction in bone can be divided into four distinct stages, i.e., mechanocoupling, biochemical coupling, the transmission of biochemical signals, and effector cell response [10]. Mechanocoupling, the transduction of mechanical energy, is executed by cells in mechanosensory molecular complexes. Biochemical coupling refers to the detection and conversion of mechanical stimuli into biochemical signals in the cell. One possible conversion mechanism is via the extracellular matrix-integrin-cytoskeletal axis [8]. Cells attach to their substrate through membrane-spanning glycoproteins (integrins). Integrin-a5 is of specific interest for osteoblasts and osteocytes, since it may open hemichannels and release prostaglandins in osteocytes treated by shear stress [11,12]. Moreover, integrin-a5 is required for osteoblast differentiation [13]. Integrins connect the extracellular matrix to the cytoskeleton,
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