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Metabolic regulation of skeletal cell fate and function in physiology and disease

Nature Metabolism volume 3, pages 11–20 (2021)Cite this article

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Abstract

The skeleton is diverse in its functions, which include mechanical support, movement, blood cell production, mineral storage and endocrine regulation. This multifaceted role is achieved through an interplay of osteoblasts, chondrocytes, bone marrow adipocytes and stromal cells, all generated from skeletal stem cells. Emerging evidence shows the importance of cellular metabolism in the molecular control of the skeletal system. The different skeletal cell types not only have distinct metabolic demands relating to their particular functions but also are affected by microenvironmental constraints. Specific metabolites control skeletal stem cell maintenance, direct lineage allocation and mediate cellular communication. Here, we discuss recent findings on the roles of cellular metabolism in determining skeletal stem cell fate, coordinating osteoblast and chondrocyte function, and organizing stromal support of haematopoiesis. We also consider metabolic dysregulation in skeletal ageing and degenerative diseases, and provide an outlook on how the field may evolve in the coming years.

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Fig. 1: Overview of the main skeletal cell types.
Fig. 2: Current understanding of skeletal cell metabolism.
Fig. 3: Metabolic communication between stromal and blood cells in the bone marrow niche.
Fig. 4: Metabolic effects of ageing on skeletal cells.
Fig. 5: Moving toward a more comprehensive understanding of skeletal cell metabolism.

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Acknowledgements

N.v.G. is supported by a Young Investigator Award from Alex’s Lemonade Stand Foundation for Childhood Cancer and Tap Cancer Out, and by funding from the de Duve Institute. G.C. receives funding from FWO G0B3418 and G0C5120, KUL-C24/17/077.

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Authors and Affiliations

  1. de Duve Institute, Brussels, Belgium

    Nick van Gastel

  2. Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA

    Nick van Gastel

  3. Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium

    Geert Carmeliet

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N.v.G. and G.C. conceived the idea, wrote and revised the manuscript and approved the final version; N.v.G. prepared the figures.

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Correspondence to Nick van Gastel or Geert Carmeliet.

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Peer review information Primary Handling Editors: Christoph Schmitt; Pooja Jha. Nature Metabolism thanks Ryan C. Riddle, Erica Scheller and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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van Gastel, N., Carmeliet, G. Metabolic regulation of skeletal cell fate and function in physiology and disease. Nat Metab 3, 11–20 (2021). https://doi.org/10.1038/s42255-020-00321-3

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