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The microbiome adds to the complexity of parathyroid hormone action on bone
Sundeep Khosla
Sundeep Khosla
Published March 3, 2020
Citation Information: J Clin Invest. 2020;130(4):1615-1617. https://doi.org/10.1172/JCI135712.
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The microbiome adds to the complexity of parathyroid hormone action on bone

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Abstract

Parathyroid hormone (PTH) has complex effects on bone, including stimulating bone formation and regulating the hematopoietic stem cell (HSC) niche. In the current issue of the JCI, Li et al. demonstrated that the microbiome, through the production of short-chain fatty acids and in particular, butyrate, is necessary for the ability of PTH to increase osteoblast numbers and stimulate bone formation. In addition to implications for the treatment of osteoporosis with PTH analogs, this pathway may be part of a broader mechanism through which the microbiome serves its key function of modulating the immune system.

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Sundeep Khosla

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Figure 1

Model for interactions between the gut microbiome and PTH signaling, converging with HSC regulation.

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Model for interactions between the gut microbiome and PTH signaling, con...
Butyrate produced by the gut microbiota binds to the GPR43 receptor on dendritic cells (DC) and also acts directly on CD4+ T cells independently of GPR43 signaling. PTH signals through the PTH1R on CD4+ T cells, and butyrate acts in concert with PTH to differentiate CD4+ T cells into Tregs which, in turn, stimulate CD8+ T cells to produce Wnt10b (4). Wnt10b acts on osteoprogenitor cells, leading to their expansion and differentiation (9), resulting in a net increase in osteoblasts on bone surfaces and increased bone formation as well as increased bone volume fraction. Osteoblasts also form part of the niche for the self-renewal and expansion of HSCs (3). In addition, the Wnt10b produced by T cells leads to the self-renewal of HSCs (14). Independent of this pathway, microbiota also lead to an expansion of HSCs (13), which require the osteoblast niche cells generated by the microbiome-PTH axis.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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