Osteoblast Differentiation at a Glance

Abstract

Ossification is a tightly regulated process, performed by specialized cells called osteoblasts. Dysregulation of this process may cause inadequate or excessive mineralization of bones or ectopic calcification, all of which have grave consequences for human health. Understanding osteoblast biology may help to treat diseases such as osteogenesis imperfecta, calcific heart valve disease, osteoporosis, and many others. Osteoblasts are bone-building cells of mesenchymal origin; they differentiate from mesenchymal progenitors, either directly or via an osteochondroprogenitor. The direct pathway is typical for intramembranous ossification of the skull and clavicles, while the latter is a hallmark of endochondral ossification of the axial skeleton and limbs. The pathways merge at the level of preosteoblasts, which progress through 3 stages: proliferation, matrix maturation, and mineralization. Osteoblasts can also differentiate into osteocytes, which are stellate cells populating narrow interconnecting passages within the bone matrix.The key molecular switch in the commitment of mesenchymal progenitors to osteoblast lineage is the transcription factor cbfa/runx2, which has multiple upstream regulators and a wide variety of targets. Upstream is the Wnt/Notch system, Sox9, Msx2, and hedgehog signaling. Cofactors of Runx2 include Osx, Atf4, and others. A few paracrine and endocrine factors serve as coactivators, in particular, bone morphogenetic proteins and parathyroid hormone. The process is further fine-tuned by vitamin D and histone deacetylases. Osteoblast differentiation is subject to regulation by physical stimuli to ensure the formation of bone adequate for structural and dynamic support of the body. Here, we provide a brief description of the various stimuli that influence osteogenesis: shear stress, compression, stretch, micro- and macrogravity, and ultrasound. A complex understanding of factors necessary for osteoblast differentiation paves a way to introduction of artificial bone matrices.

An overview on osteogenic differentiation process: Minimum essential information for bone tissue engineering

“…The remodeling process includes three distinct phases: the digestion of old bone by osteoclasts, the appearance of cells on the bone surface and the renewal of the bone (Hadjidakis and Androulakis, 2006). Osteoblasts together with osteoclasts are responsible for mediating these processes (Rutkovskiy et al, 2016). The differentiation process of stem cells into mature osteocytes includes more steps: (1.)…”

“…the mineralization of the matrix which is produced by mature osteoblasts and osteocytes (Jayakumar et al, 2010). The MSCs present a multipotent character which underlies their capacity to give rise to myoblasts, osteoblasts, chondrocytes and adipocytes (Rutkovskiy et al, 2016). Each lineage is controlled by so called "master transcriptional regulators" (Rutkovskiy et al, 2016), that are essential for each differentiation process.…”

“…The MSCs present a multipotent character which underlies their capacity to give rise to myoblasts, osteoblasts, chondrocytes and adipocytes (Rutkovskiy et al, 2016). Each lineage is controlled by so called "master transcriptional regulators" (Rutkovskiy et al, 2016), that are essential for each differentiation process. Myoblast Determination Protein is for the myoblast lineage, Sex determining region of the Y-box 9 is for the chondroblast lineage, Peroxisome proliferator-activated receptor gamma for the adipocyte lineage and Runt-related transcription factor 2 (RUNX2) for the osteoblast lineage (Rutkovskiy et al, 2016).…”

“…Each lineage is controlled by so called "master transcriptional regulators" (Rutkovskiy et al, 2016), that are essential for each differentiation process. Myoblast Determination Protein is for the myoblast lineage, Sex determining region of the Y-box 9 is for the chondroblast lineage, Peroxisome proliferator-activated receptor gamma for the adipocyte lineage and Runt-related transcription factor 2 (RUNX2) for the osteoblast lineage (Rutkovskiy et al, 2016). As soon as RUNX2 is activated, the cells begin the differentiation process undergoing more stages, each stage being characterized by particular molecular markers (Rutkovsky et al, 2016).…”

“…They remain present throughout life, but are not as active as they are during embryogenesis. Only in case of an injury in an adult organism osteoblasts are activated for the regeneration process (Rutkovskiy et al, 2016). Osteoblasts have a slow response: it takes four months for a mature osteoblast to synthesize bone matrix (Rutkovskiy et al, 2016).…”