Abstract
Bone formation starts near the end of the embryonic stage of development and continues throughout life during bone modeling and growth, remodeling, and when needed, regeneration. Bone-forming cells, traditionally termed osteoblasts, produce, assemble, and control the mineralization of the type I collagen-enriched bone matrix while participating in the regulation of other cell processes, such as osteoclastogenesis, and metabolic activities, such as phosphate homeostasis. Osteoblasts are generated by different cohorts of skeletal stem cells that arise from different embryonic specifications, which operate in the pre-natal and/or adult skeleton under the control of multiple regulators. In this review, we briefly define the cellular identity and function of osteoblasts and discuss the main populations of osteoprogenitor cells identified to date. We also provide examples of long-known and recently recognized regulatory pathways and mechanisms involved in the specification of the osteogenic lineage, as assessed by studies on mice models and human genetic skeletal diseases.
Highlights
Many advances have been made over the last few years in the field of bone biology.They have not overtly changed our concept of bone-forming cells, which has remained firmly rooted in classic topographic, morphological, and functional criteria, but have led to the emergence of new and exciting paradigms regarding their origin and differentiation
The mature skeleton is comprised of multiple tissues including cartilage, bone, marrow stroma, and marrow fat that appear during skeletal ontogeny in an asynchronous manner, with cartilage and bone being the first and marrow stroma and fat the last
Interesting results on the molecular targets and mechanisms of action of the transforming growth factor βs (TGFβs)/bone morphogenetic proteins (BMPs) system in osteoblastogenesis come from in vitro studies with human and mouse cells. These studies provide a detailed analysis of the gene expression profile of immortalized human bone marrow stromal cells during BMP-dependent osteogenic differentiation [114], and they show that BMP2 is able to stimulate Osx expression through a RUNX2-dependent and
Summary
Many advances have been made over the last few years in the field of bone biology. They have not overtly changed our concept of bone-forming cells, which has remained firmly rooted in classic topographic, morphological, and functional criteria, but have led to the emergence of new and exciting paradigms regarding their origin and differentiation. Emerging concepts in skeletal stem cell biology and osteoblastogenesis are presented. We first summarize the steps that occur during bone development and continue with a discussion on the canonical bone marrow skeletal stem cell system and other cell types that have been recently identified as sources of bone-forming cells. We discuss new insights recently reported into the role played by osteoclasts as modulators of osteoblast differentiation
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