Page 164 - Physico-Chemical Niche Conditions for Bone Cells

General discussion
GENERAL DISCUSSION
Bone is a heterogeneous and dynamic organ consisting of a highly plastic and complex microenvironment, populated by different cell populations, containing mineralized or nonmineralized tissues, cytokines, hormones, and nutrients [1]. Under homeostatic conditions, cytokines and growth factors (e.g. basic fibroblast growth factor, transforming growth factor b), hormones (e.g. estrogen, androgen, parathyroid hormone), and nutrients (e.g. minerals, glucose, vitamins) play pivotal roles in bone development, remodeling, and regeneration. They balance interactions between different cell types in a dynamic environment [2–4]. In contrast, inflammatory cytokines (e.g. interleukins, interferon g, tumor necrosis factor a), hormonal disorders (e.g. excessive glucocorticoids, estrogen deficiency), and nutritional imbalance (e.g. hyperglycemia) impair the balance between different cell types, resulting in the emergence, occurrence, and progression of bone diseases [2,5–7]. Additionally, during orthodontic tooth movement, tension forces promote bone formation and angiogenesis [8]. In contrast, compression forces induce cell damage, hypoxia, necrosis, and bone resorption. Bone formation or resorption around the teeth in jaw bone depend on the types of strain applied [8]. Therefore, it is of utmost importance to understand how homeostasis can be maintained within the complex bone environment.
Physical and/or (bio)chemical factors can affect the bone cell response and function [9,10]. Physical factors, such as spinal loading, significantly promote osteoblast differentiation, bone mineral content, bone mineral density, and bone area per tissue area in a postmenopausal osteoporosis mouse model [11]. After spinal loading, (bio)chemical factors, such as Wnt3a, are affected in osteoblasts, resulting in improved microvascular volume and VEGF expression in this model [11]. Therefore, the main goal of this thesis was to investigate the effect of physical and (bio)chemical niche conditions on the (pre)-osteoblast mechanoresponse and behavior. In this thesis, a physical factor (pulsating fluid flow (PFF)) and (bio)chemical factors (nitric oxide (NO), fibroblast growth factor 2 (Fgf2), Wnt signaling factors, and arginine-glycine-aspartate (RGD)) were evaluated for their effect on the MC3T3- E1 pre-osteoblast mechanoresponse and behavior. The aims of the studies presented in this thesis were:
1. To review the physicochemical niche conditions of (pre)-osteocytes and myocytes, and how
these niche conditions affect the manner in which mechanical cues are sensed, thereby
determining cell fate and function (Chapter 2).
2. To investigate whether PFF, as model for a physical niche condition, induces changes in
three-dimensional (3D) cell and nucleus morphology and function of osteoblasts, and how
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