Hypertension promotes bone loss and fragility by favoring bone resorption in mouse models
Elizabeth M. Hennen, Sasidhar Uppuganti, Néstor de la Visitación, Wei Chen, Jaya Krishnan, Lawrence A. Vecchi III, David M. Patrick, Mateusz Siedlinski, Matteo Lemoli, Rachel Delgado, Mark P. de Caestecker, Wenhan Chang, Tomasz J. Guzik, Rachelle W. Johnson, David G. Harrison, Jeffry S. Nyman
Elizabeth M. Hennen, Sasidhar Uppuganti, Néstor de la Visitación, Wei Chen, Jaya Krishnan, Lawrence A. Vecchi III, David M. Patrick, Mateusz Siedlinski, Matteo Lemoli, Rachel Delgado, Mark P. de Caestecker, Wenhan Chang, Tomasz J. Guzik, Rachelle W. Johnson, David G. Harrison, Jeffry S. Nyman
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Research Article Bone biology Immunology Inflammation

Hypertension promotes bone loss and fragility by favoring bone resorption in mouse models

Abstract

Inflammatory diseases contribute to secondary osteoporosis. Hypertension is a highly prevalent inflammatory condition that is clinically associated with reduced bone mineral density and increased risk of fragility fracture. In this study, we showed that a significant loss in bone mass and strength occurs in two preclinical models of hypertension. This accompanied increases in immune cell populations, including monocytes, macrophages, and IL-17A–producing T cell subtypes in the bone marrow of hypertensive mice. Neutralizing IL-17A in angiotensin II–infused mice blunted hypertension-induced loss of bone mass and strength as a result of decreased osteoclastogenesis. Likewise, the inhibition of the CSF1 receptor blunted loss of bone mass and prevented loss of bone strength in hypertensive mice. In an analysis of UK Biobank data, circulating bone remodeling markers exhibited striking associations with blood pressure and bone mineral density in more than 27,000 humans. These findings illustrate a potential mechanism by which hypertension activates immune cells in the bone marrow, encouraging osteoclastogenesis and eventual loss in bone mass and strength.

Authors

Elizabeth M. Hennen, Sasidhar Uppuganti, Néstor de la Visitación, Wei Chen, Jaya Krishnan, Lawrence A. Vecchi III, David M. Patrick, Mateusz Siedlinski, Matteo Lemoli, Rachel Delgado, Mark P. de Caestecker, Wenhan Chang, Tomasz J. Guzik, Rachelle W. Johnson, David G. Harrison, Jeffry S. Nyman

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Figure 9

Analysis of osteoclasts in the bone and bone marrow from Ang II–infused IgG- or α-IL-17A–treated mice.

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Analysis of osteoclasts in the bone and bone marrow from Ang II–infused ...
(A) H&E-stained and TRAP-stained sections at 2 views (original magnification, ×4 at left and ×20 at right). Left scale bars: 200 μm; right scale bars: 50 μm. (B–D) Quantification of differences in osteoclast number (B) or surface (C) and osteoblast number (D). (E) The concentration of CSF1 in the bone marrow. (F) The concentration of RANKL in the bone marrow. (G) The relative expression of osteoclast-related transcripts. B–E were analyzed by unpaired t test. F and G were analyzed by Mann-Whitney test. SEM is shown. Sample size: IgG, n = 5–7; α-IL-17A, n = 6–10.