Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis
The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis....
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/414 |
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| author | Saja Baraghithy Yael Soae Dekel Assaf Liad Hinden Shiran Udi Adi Drori Yankel Gabet Joseph Tam |
| author_facet | Saja Baraghithy Yael Soae Dekel Assaf Liad Hinden Shiran Udi Adi Drori Yankel Gabet Joseph Tam |
| author_sort | Saja Baraghithy |
| collection | DOAJ |
| description | The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB<sub>1</sub>R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB<sub>1</sub>R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB<sub>1</sub>R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB<sub>1</sub>R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO. |
| first_indexed | 2024-03-09T00:48:53Z |
| format | Article |
| id | doaj.art-b51fc7c41fed4fefa7cb850b030a9c1e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:48:53Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b51fc7c41fed4fefa7cb850b030a9c1e2023-12-11T17:19:29ZengMDPI AGCells2073-44092021-02-0110241410.3390/cells10020414Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone AxisSaja Baraghithy0Yael Soae1Dekel Assaf2Liad Hinden3Shiran Udi4Adi Drori5Yankel Gabet6Joseph Tam7Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelDepartment of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelThe renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB<sub>1</sub>R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB<sub>1</sub>R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB<sub>1</sub>R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB<sub>1</sub>R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.https://www.mdpi.com/2073-4409/10/2/414type 1 diabetesosteoporosisCB1 receptorerythropoietin |
| spellingShingle | Saja Baraghithy Yael Soae Dekel Assaf Liad Hinden Shiran Udi Adi Drori Yankel Gabet Joseph Tam Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis Cells type 1 diabetes osteoporosis CB1 receptor erythropoietin |
| title | Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis |
| title_full | Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis |
| title_fullStr | Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis |
| title_full_unstemmed | Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis |
| title_short | Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis |
| title_sort | renal proximal tubule cell cannabinoid 1 receptor regulates bone remodeling and mass via a kidney to bone axis |
| topic | type 1 diabetes osteoporosis CB1 receptor erythropoietin |
| url | https://www.mdpi.com/2073-4409/10/2/414 |
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