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Building strong bones: molecular regulation of the osteoblast lineage

Nature Reviews Molecular Cell Biology volume 13, pages 27–38 (2012)Cite this article

Subjects

Key Points

  • Bones have important endocrine and paracrine roles beyond their structural function.

  • Bone mass and integrity is determined by the opposing activities of osteoblasts (which make bone) and osteoclasts (which resorb bone).

  • Osteoblasts are derived progressively from mesenchymal progenitors and preosteoblasts, and can further become bone-lining cells and osteocytes. These cells are collectively called osteoblast lineage cells.

  • Differentiation of osteoblasts from mesenchymal progenitors requires the activities of stage-specific transcription factors.

  • Osteoblast differentiation is regulated by a range of developmental signals, which control specific stages of the progression along the osteoblast lineage.

  • Bone homeostasis is controlled by a range of hormones.

Abstract

The past 15 years have witnessed tremendous progress in the molecular understanding of osteoblasts, the main bone-forming cells in the vertebrate skeleton. In particular, all of the major developmental signals (including WNT and Notch signalling), along with an increasing number of transcription factors (such as RUNX2 and osterix), have been shown to regulate the differentiation and/or function of osteoblasts. As evidence indicates that osteoblasts may also regulate the behaviour of other cell types, a clear understanding of the molecular identity and regulation of osteoblasts is important beyond the field of bone biology.

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Figure 1: Osteoclast and osteoblast lineage cells.
Figure 2: The different stages of osteoblast lineage cell differentiation.
Figure 3: Developmental signals regulating key steps of osteoblast differentiation.

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Acknowledgements

Work in the author's laboratory is supported by US National Institutes of Health grants AR055923, DK065789 and AR060456. The author apologizes for the omission of many references owing to space limitations.

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  1. Departments of Medicine and Developmental Biology, Washington University School of Medicine, St Louis, 63110, Missouri, USA

    Fanxin Long

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Glossary

Cortical bone

The compact hard tissue that forms the outer shell of a bone and surrounds the marrow cavity.

Periosteum

The layered fibrous membrane covering the surface of bone tissue. It contains osteoblast progenitors.

Axial skeleton

Bones that form the central axis of the body, including the bones of the skull, the vertebrae, the ribs and the sternum.

Appendicular skeleton

The bones of the limbs, the shoulders and the hip girdles.

Somites

Mesodermal structures found on either side of the neural tube in vertebrate embryos that eventually give rise to muscle, skin and vertebrae.

Clavicle

The collar bone, connecting the scapula and the sternum.

Primordium

An organ or tissue at its earliest stages of development; also known as the anlage.

Fontanelles

Membrane-covered spaces (soft spots) between adjacent bones in a newborn's skull.

Cleidocranial dysplasia

A human autosomal-dominant disorder with persistently open skull sutures and bulging calvaria, hypoplasia or aplasia of the clavicles. The disorder is caused by loss-of-functions mutations in RUNX2.

Perichondrium

The layered fibrous membrane covering the surface of cartilage. Cells residing within the perichondrium, including osteoblast progenitors, are termed perichondrial cells.

Trabecular bone

Compared with cortical bone, the porous and less dense bone tissue found at the ends of long bones and within the interior of vertebrae.

Hadju–Cheney syndrome

A rare autosomal-dominant inherited disorder characterized by craniofacial abnormalities and generalized osteoporosis. Caused by truncating mutations in exon 34 of NOTCH2.

Osteopenia

A condition in which bone mineral density is lower than normal but not low enough to be considered osteoporosis.

Osteoporosis-pseudoglioma syndrome

A human autosomal-recessive disorder that is characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness. Caused by loss-of-function mutations in low-density lipoprotein receptor-related protein 5 (LRP5).

Sclerosteosis

A rare autosomal-recessive disorder that is characterized by generalized bone thickening (mostly pronounced in the skull and the mandible), tall stature and hand malformations. Caused by loss-of-function mutations in SOST.

Van Buchem disease

A rare autosomal-recessive disorder that is characterized by generalized bone thickening, similar to sclerosteosis but without the tall stature or hand malformations. Caused by a deletion downstream of SOST.

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Long, F. Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 13, 27–38 (2012). https://doi.org/10.1038/nrm3254

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