From Stem Cells to Bone-Forming Cells

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.

Keywords: bone; bone marrow stromal cells; osteoblasts; skeletal biology; skeletal stem cells.

Figure 1

Osteoblasts rimming a bone trabecula with unmineralized (asterisk) and mineralized matrix with embedded osteocytes (arrow). Formalin-fixed, non-decalcified plastic-embedded tissue, May-Grünwald-Giemsa. Scale bar: 25 µm.

Figure 2

ALP histochemistry showing osteogenic cells in the periosteum (arrows) and within the marrow cavity (asterisks) in the developing femur of an E18 mouse embryo. Right panel represents the boxed region in the left panel. Formalin fixed tissue embedded in optimal cutting temperature (OCT) compound after decalcification. Scale bars: 100 µm and 50 µm in the left and right panel, respectively.

Figure 3

Abnormally shaped (i.e., retracted, arrows) osteoblasts and excessive unmineralized bone matrix (asterisks) in Fibrous Dysplasia (FD) bone. Formalin-fixed undecalcified plastic-embedded sample, Von Kossa-Methylene Blue. Bar: 50 µm.

Figure 4

Left panel: Long bone skeletal compartments that host different subsets of stem/progenitor cells. Hypertrophic chondrocytes may also differentiate into bone forming cells. Right panel: Osteoclasts modulate osteogenic differentiation and osteoblast function by secreting regulatory factors and membrane-coated vesicles and by establishing cell–cell contacts with osteogenic cells.