The influence of TRAIL, adiponectin and sclerostin alterations on bone loss in BDL-induced cirrhotic rats and the effect of opioid system blockade.

Abstract

AIMS:

Osteoporosis is a common extra-hepatic complication in patients with chronic liver disease. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), sex hormones, adiponectin, and sclerostin are involved in the regulation of bone turnover but little is known about their role in the promotion of hepatic osteodystrophy. Endogenous opioids are reported to increase during cholestasis and may influence bone resorption. The purpose of this study was to investigate the circulating levels of these factors and their expression in the femur of bile duct ligated (BDL) rats, to evaluate the biomechanical bone strength, and the effect of naltrexone (NTX).

MATERIALS AND METHODS:

BDL and sham-operated (SO) rats received 10 mg/kg NTX as an opioid-receptors antagonist or saline once daily for 28 days intraperitoneally. Three-point bending test was performed on the right femurs and, plasma bone alkaline phosphatase (BALP), sex hormones, TRAIL, adiponectin, sclerostin, as well as the mRNA expression levels of the latter three proteins, were measured in the femur tissues.

KEY FINDINGS:

Plasma TRAIL, estrogen, adiponectin, sclerostin and, BALP levels increased in BDL animals when compared to the related controls, whereas testosterone level decreased and NTX reversed these effects significantly. Femur strength decreased in cirrhotic animals and interestingly, blocking opioid-receptors by NTX improved it significantly (p ≤ 0.05).

SIGNIFICANCE:

High levels of TRAIL, adiponectin and, sclerostin after bile duct ligation, suggest that these factors may have some roles in bone loss after cirrhosis. Administration of NTX improved all the mentioned factors except for bone strength. Effect of NTX on bone loss in BDL rats needs more study to clarify.

• Authors: Mona Moradi, Amir Hossein Doustimotlagh, Ahmad Reza Dehpour, Nastaran Rahimi, Abolfazl Golestani
• Journal: Life sciences (Life Sci) Vol. 233 Pg. 116706 (Sep 15 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31369758 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adiponectin
• Adipoq protein, rat
• Bone Morphogenetic Proteins
• Genetic Markers
• Narcotic Antagonists
• Receptors, Opioid
• Sost protein, rat
• TNF-Related Apoptosis-Inducing Ligand
• Tnfsf10 protein, rat
• Naltrexone

Topics

• Adiponectin (blood)
• Animals
• Bile Ducts (surgery)
• Bone Morphogenetic Proteins (blood)
• Bone Resorption (blood, pathology)
• Genetic Markers
• Ligation
• Liver Cirrhosis, Biliary (blood, drug therapy, etiology, pathology)
• Male
• Naltrexone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid (chemistry)
• TNF-Related Apoptosis-Inducing Ligand (blood)