薬理と治療

Abstract

Objectives　Hypertriglyceridemia was shown to be a risk factor for bone fractures by SWAN study. We previously reported that hypertriglyceridemia contributes to a lower bone density in type 2 diabetic patients and confirmed that hypertriglyceridemia is a risk factor for osteopenia and bone fractures. Fibrate agents, peroxisome proliferator-activated receptor alpha（PPARα）-agonists, have a strong effect to reduce plasma TG levels. Although the previous reports have shown the causal relation of hypertriglyceridemia on osteopenia, there are few data concerning the effect of fibrate agents on bone disease. In the present study we examined the effects of fenofibrate on TG-rich lipoproteins-loaded osteoblastic cells. Methods　TG-rich lipoproteins was collected from plasma by density gradient ultracentrifugation. Normal human osteoblastic cells were cultured, and were loaded with TG-rich lipoproteins. Fenofibrate was added to TG-rich lipoproteins-loaded human osteoblastic cells at a concentration of 50, 100, or 300μmol╱L, and after 6 hours of incubation, total RNA was isolated for analysis. The mRNA expression of PPARα, RANKL, Type 1 collagen, Runx2 and Twist was quantified by RT-PCR. Results　The addition of fenofibrate in TG-rich lipoproteins-loaded osteoblastic cells significantly decreased RANKL mRNA expression and significantly increased Type 1 collagen mRNA expression in a concentration-dependent manner. The addition of fenofibrate significantly increased Runx2 mRNA expression and significantly decreased Twist mRNA expression in a concentration-dependent manner. Conclusion　Fenofibrate has beneficial and protective effects on bone loss through a plasma TG-lowering action and a direct action on osteoblastis in patients with hypertriglyceridemia and diabetes. （Jpn Pharmacol Ther 2022；50：2151‒6）