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The endothelium–bone axis in development, homeostasis and bone and joint disease

Nature Reviews Rheumatology volume 17, pages 608–620 (2021)Cite this article

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Abstract

Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed.

Key points

  • The vascular system is essential for bone development and growth.

  • Capillary endothelial cells consist of multiple subpopulations with distinct molecular and functional properties.

  • The type H endothelial subpopulation communicates with chondrocytes and perivascular osteoblast lineage cells during development and fracture repair, and type H capillaries are reduced in ageing and osteoporosis.

  • Blood vessels influence the behaviour of fibroblast-like synoviocytes and macrophages in the arthritic joint.

  • Pre-osteoclasts secrete factors that affect bone angiogenesis and the abundance of type H endothelial cells.

  • Interdependent crosstalk between endothelial cells and other cell populations in bone might provide novel entry points for anti-osteoporotic therapy.

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Fig. 1: Organization of the bone vasculature during development.
Fig. 2: Blood flow in long bones.
Fig. 3: Osteoclast–endothelial cell crosstalk.
Fig. 4: Vasculature, fibroblast-like synoviocyte and macrophage interactions in RA.
Fig. 5: Remodelling of the bone vasculature in adult life and ageing.

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Acknowledgements

The work of R.H.A. is supported by the Max Planck Society, the European Research Council (AdG 786672, PROVEC) and the Leducq Foundation. The work of J.T. is supported by the Deutsche Forschungsgemeinschaft (Tu220/12, Tu220/14-1, Ci 216/2).

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Authors and Affiliations

  1. Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany

    Jan Tuckermann

  2. Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, University of Münster, Faculty of Medicine, Münster, Germany

    Ralf H. Adams

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The authors contributed equally to all aspects of the article.

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Correspondence to Jan Tuckermann or Ralf H. Adams.

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Competing interests

R.H.A. declares that he is an investigator on patent EP 2 860 243 A1 (Reprogramming bone endothelial cells for bone angiogenesis and osteogenesis). J.T. declares no competing interests.

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Nature Reviews Rheumatology thanks A. Naylor, R. Prisby and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Gorham–Stout disease

A rare osteolytic disease that is causally linked to the overgrowth and invasion of lymphatic vessels.

Epiphysis

Rounded portion at the end of a long bone that ossifies separately and is typically part of a joint.

Metaphysis

The section of the bone that mediates growth (length extension) and the connection between the diaphysis and epiphysis.

Diaphysis

The midsection (shaft) of long bone, which is enclosed by cortical bone and harbours bone marrow.

Ring of La Croix

A perichondral structure that surrounds the growth plate laterally.

Secondary spongiosa

The region where newly formed bony trabeculae are remodelled into mature trabeculae.

Primary spongiosa

The site near the growth plate where trabecular bone formation is initiated.

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Tuckermann, J., Adams, R.H. The endothelium–bone axis in development, homeostasis and bone and joint disease. Nat Rev Rheumatol 17, 608–620 (2021). https://doi.org/10.1038/s41584-021-00682-3

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