# Static Osteogenesis versus Dynamic Osteogenesis:
## 2 Structural and Functional Differences between SO and DO
Figure 2: A diagram showing an osteoblastic lamina during DO. From left to right, the osteoblastic lamina moves away (as indicated by black arrows) from the mineralized front (green bar) to the vessels (red circles). The white arrows indicate the osteoblast polarization side. Two generations of almond-like shaped osteocytes (located in planes) are enclosed inside the bone (see text for further details). with respect to the adjacent ones, and give rise to osteocytes at the same site where they previously differentiated (Figure 3). A further distinctive feature of these osteoblasts is their presence in a \"symmetrical\" environment: this differentiates them from those arranged in the typical laminae during DO, which are located in an \"asymmetrical\" domain (see above). With regard to morphology, SO osteocytes retain approximately the same globous shape and ultrastructure of the parental stationary osteoblasts; moreover, they are often located inside confluent lacunae in the core of the thin bony trabeculae (about 10-15 \(\upmu\)m thick), formed only by 2-3 irregular rows/groups of osteocytes. Their dendrites are also shorter than those of DO osteocytes and radiate simultaneously (not in an asynchronous manner as in DO) all around the cell body (Figure 4). At first, the dendrites are so short as to look like spines; afterward, some of them elongate, but only marginally, because their parental osteoblasts are practically stationary, withdrawing from one another by just a few mica. The resulting osteocyte arrangement, which is haphazard and clustered, is dependent on the peculiar recruitment in groups and, in turn, influences the collagen texture, resulting in woven bone (Figure 5). Because the secretory territories of SO stationary osteoblasts are randomly oriented, the matrix is highly porous, and the orientation of the collagen fibers, while uniform at the cellular level [9], is random at larger scales. Gap junctions or simple contacts are observed between stationary osteoblasts and between the spines and dendrites of SO osteocytes [10]. In addition to the prior differences, SO and DO have different conditioning factors. An intriguing problem is the differentiation of stationary osteoblasts at a certain distance from the vessels; SO allows the formation of a preliminary trabecular bony framework enclosing the blood vessels. This is essential for the subsequent bone appposition by DO. In a previous paper of ours [11], when comparing intramembranous and endochondral ossifications, the following crucial differences between SO and DO clearly emerged. During intramembranous ossification center development, bone growth occurs by progressive extension of stationary osteoblastic cords inside the surrounding mesenchyme, fairly constantly at about midway between blood capillaries (mean distance of cords from vessels, 28 \(\pm\) 0.4 \(\upmu\)m). Recently, in a study on regeneration with bone substitutes, the intimate functional connection between blood vessels and bone formation highlighted the combined interaction between the mesenchymal stem cell secretome (extracellular vesicles) and microRNAs [12]. How  
Figure 3: Drawings showing stationary osteoblasts, irregularly arranged in cords, that differentiate among the vessels (red circles). Inside the cords, osteoblasts are polarized in different directions with respect to the adjacent ones (**A**) and give rise to osteocytes (**B**) at the same site where they previously differentiated. ECGF: endothelial cell growth factor; HIF: hypoxia-inducible factor; PDGF: platelet-derived growth factor; EDGF: endothelial-derived growth factor. ever, this fact does not explain the mechanism by which mesenchymal cells (transforming into preosteoblasts) \"sense\" the position of the vessels. Several factors may be involved, such as O2 tension [13; 14], endothelial cell-derived cytokines (i.e., endothelin-1) [15; 16; 17], and growth factors (EDGF, ECGF) [18; 19; 20; 21].