Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice
The intake of dietary phosphate far exceeds recommended levels; however, the long-term health consequences remain relatively unknown. Here, the chronic physiological response to sustained elevated and reduced dietary phosphate consumption was investigated in mice. Although serum phosphate levels wer...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-05-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.154729 |
| _version_ | 1797634315158290432 |
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| author | Joseph L. Roberts Mingcan Yu Manjula Viggeswarapu Jamie L. Arnst Roberto Pacifici George R. Beck Jr |
| author_facet | Joseph L. Roberts Mingcan Yu Manjula Viggeswarapu Jamie L. Arnst Roberto Pacifici George R. Beck Jr |
| author_sort | Joseph L. Roberts |
| collection | DOAJ |
| description | The intake of dietary phosphate far exceeds recommended levels; however, the long-term health consequences remain relatively unknown. Here, the chronic physiological response to sustained elevated and reduced dietary phosphate consumption was investigated in mice. Although serum phosphate levels were brought into homeostatic balance, the prolonged intake of a high-phosphate diet dramatically and negatively impacted bone volume; generated a sustained increase in the phosphate responsive circulating factors FGF23, PTH, osteopontin and osteocalcin; and produced a chronic low-grade inflammatory state in the BM, marked by increased numbers of T cells expressing IL-17a, RANKL, and TNF-α. In contrast, a low-phosphate diet preserved trabecular bone while increasing cortical bone volume over time, and it reduced inflammatory T cell populations. Cell-based studies identified a direct response of T cells to elevated extracellular phosphate. Neutralizing antibodies against proosteoclastic cytokines RANKL, TNF-α, and IL-17a blunted the high-phosphate diet–induced bone loss identifying bone resorption as a regulatory mechanism. Collectively, this study illuminates that habitual consumption of a high-phosphate diet in mice induces chronic inflammation in bone, even in the absence of elevated serum phosphate. Furthermore, the study supports the concept that a reduced phosphate diet may be a simple yet effective strategy to reduce inflammation and improve bone health during aging. |
| first_indexed | 2024-03-11T12:05:54Z |
| format | Article |
| id | doaj.art-ad4a4086c828464eac336155a4505759 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:05:54Z |
| publishDate | 2023-05-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-ad4a4086c828464eac336155a45057592023-11-07T16:25:39ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-05-01810Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in miceJoseph L. RobertsMingcan YuManjula ViggeswarapuJamie L. ArnstRoberto PacificiGeorge R. Beck JrThe intake of dietary phosphate far exceeds recommended levels; however, the long-term health consequences remain relatively unknown. Here, the chronic physiological response to sustained elevated and reduced dietary phosphate consumption was investigated in mice. Although serum phosphate levels were brought into homeostatic balance, the prolonged intake of a high-phosphate diet dramatically and negatively impacted bone volume; generated a sustained increase in the phosphate responsive circulating factors FGF23, PTH, osteopontin and osteocalcin; and produced a chronic low-grade inflammatory state in the BM, marked by increased numbers of T cells expressing IL-17a, RANKL, and TNF-α. In contrast, a low-phosphate diet preserved trabecular bone while increasing cortical bone volume over time, and it reduced inflammatory T cell populations. Cell-based studies identified a direct response of T cells to elevated extracellular phosphate. Neutralizing antibodies against proosteoclastic cytokines RANKL, TNF-α, and IL-17a blunted the high-phosphate diet–induced bone loss identifying bone resorption as a regulatory mechanism. Collectively, this study illuminates that habitual consumption of a high-phosphate diet in mice induces chronic inflammation in bone, even in the absence of elevated serum phosphate. Furthermore, the study supports the concept that a reduced phosphate diet may be a simple yet effective strategy to reduce inflammation and improve bone health during aging.https://doi.org/10.1172/jci.insight.154729Bone biology |
| spellingShingle | Joseph L. Roberts Mingcan Yu Manjula Viggeswarapu Jamie L. Arnst Roberto Pacifici George R. Beck Jr Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice JCI Insight Bone biology |
| title | Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice |
| title_full | Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice |
| title_fullStr | Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice |
| title_full_unstemmed | Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice |
| title_short | Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice |
| title_sort | dietary phosphorus consumption alters t cell populations cytokine production and bone volume in mice |
| topic | Bone biology |
| url | https://doi.org/10.1172/jci.insight.154729 |
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