Renal proximal tubule cell cannabinoid-1 receptor regulates bone remodeling and mass via a kidney-to-bone axis

Saja Baraghithy, Yael Soae, Dekel Assaf, Liad Hinden, Shiran Udi, Adi Drori, Yankel Gabet, Joseph Tam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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. Deterio-ration 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 (CB1R) 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 CB1R, 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 CB1R 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 CB1R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.

Original languageAmerican English
Article number414
Pages (from-to)1-20
Number of pages20
JournalCells
Volume10
Issue number2
DOIs
StatePublished - 17 Feb 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CB1 receptor
  • Erythropoietin
  • Osteoporosis
  • Type 1 diabetes

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