Osteoblast ontogeny and implications for bone pathology: an overview

Abstract

Osteoblasts are specialized mesenchyme-derived cells accountable for bone synthesis, remodelling and healing. Differentiation of osteoblasts from mesenchymal stem cells (MSC) towards osteocytes is a multi-step process strictly controlled by various genes, transcription factors and signalling proteins. The aim of this review is to provide an update on the nature of bone-forming osteoblastic cells, highlighting recent data on MSC-osteoblast-osteocyte transformation from a molecular perspective and to discuss osteoblast malfunctions in various bone diseases. We present here the consecutive stages occurring in the differentiation of osteoblasts from MSC, the transcription factors involved and the role of miRNAs in the process. Recent data concerning the pathogenic mechanisms underlying the loss of bone mass and architecture caused by malfunctions in the synthetic activity and metabolism of osteoblasts in osteoporosis, osteogenesis imperfecta, osteoarthritis and rheumatoid arthritis are discussed. The newly acquired knowledge of the ontogeny of osteoblasts will assist in unravelling the abnormalities taking place during their differentiation and will facilitate the prevention and/or treatment of bone diseases by therapy directed against altered molecules and mechanisms.

Cystathionine γ-Lyase–Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing

“…Mature osteoblasts originate from bone marrow MSCs (33). Both CBS and CSE are expressed in MSCs, and CBS is necessary for MSC osteogenesis (26).…”

“…one formation or bone healing mainly depends on the action of two cell lineages: bone reabsorption cells (osteoclasts) and bone-forming cells (osteoblasts and their terminal differentiation cells, osteocytes, and bone-lining cells) (33). Osteoblasts play an essential role in bone synthesis, remodeling, and healing (29).…”

“…Osteoblasts play an essential role in bone synthesis, remodeling, and healing (29). Osteoblasts arise from mesenchymal stem cells (MSCs) dependent on bone morphogenetic protein (BMP) activation, runt-related transcription factor 2 (RUNX2) signaling, and other hormones (33,36). Mature osteoblasts secrete collagens (type I collagen), osteocalcin (OCN), bone sialoprotein (BSP), osteopontin (OPN), and proteoglycans such as decorin and biglycan into bone matrix (6).…”

Effect of low-intensity pulsed ultrasound on the activity of osteoclasts: An in vitro study

“…Histological findings demonstrated increased alveolar bone remodeling due to the elevated number of osteoclast (OC) cells along the bone surfaces of the moved teeth that were subjected to ultrasound application (ElBialy et al, 2011;Inubushi et al, 2013;Xue et al, 2013;Al-Daghreer et al, 2014). The LIPUS-driven increase in the OC number might be attributed to the stimulation of their differentiation as a result of an upregulation of the RANK-L gene expression in osteoblasts (Inubushi et al, 2013;Xue et al, 2013), which generates the most important mediator for osteoclastogenesis (Titorencu, Pruna, Jinga, & Simionescu, 2014).…”

Low-density lipoprotein receptor deficiency impaired mice osteoblastogenesis <i>in vitro </i>

“…Pre-osteoblasts were derived from pluripotent mesenchymal stem cells (MSCs), which were also the progenitors of adipocytes and chondrocytes (12). Osteoblastogenesis could be defined by four sequential stages: lineage commitment, proliferation, extracellular matrix (ECM) synthesis, and matrix mineralization (13). Runtrelated transcription factor 2 (Runx2) was the master transcription regulator of osteoblast lineage commitment that inhibited MSCs from differentiating into the adipocytic lineages (14).…”