Rifampicin induces the bone form of alkaline phosphatase in humans
|Author:||Nabil, Heba1,2; Kummu, Outi1,2; Lehenkari, Petri3;|
1Research Unit of Biomedicine and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Cancer Research and Translational Medicine Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
4School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
5Nordlab, Oulu University Hospital, Oulu, Finland
6Research Unit of Internal Medicine and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 0.4 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202201122012
John Wiley & Sons,
|Publish Date:|| 2022-01-12
Pregnane X receptor (PXR) is a xenobiotic-sensing nuclear receptor that regulates drug metabolism in the liver and intestine. In our clinical trials on healthy volunteers to discover novel metabolic functions of PXR activation, we observed that rifampicin, a well-established ligand for human PXR, 600 mg daily for a week, increased the plasma alkaline phosphatase (ALP) significantly compared with the placebo. Further analysis with lectin affinity electrophoresis revealed that especially the bone form of ALP was elevated. To investigate the mechanism(s) of bone ALP induction, we employed osteoblast lineage differentiated from human primary bone marrow–derived mesenchymal stromal cells. Rifampicin treatment increased ALP activity and mRNA level of bone biomarker genes (ALP, MGP, OPN and OPG). PXR expression was detected in the cells, but the expression was very low compared with the human liver. To further investigate the potential role of PXR in the ALP induction, we treated mice and rats with a rodent PXR ligand pregnenolone 16α-carbonitrile (PCN). However, PCN treatment did not increase plasma ALP activity or bone ALP mRNA expression. In conclusion, rifampicin treatment induces the bone form of ALP in the serum of healthy human volunteers. Further studies are required to establish the mechanism of this novel finding.
Basic & clinical pharmacology & toxicology
|Pages:||81 - 94|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
The Diabetes Research Foundation, the Finnish Foundation for Cardiovascular Research, the Northern Finland Health Care Support Foundation and the Finnish Medical Foundation supported the research.
© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.