Effects of Lobeglitazone, a New Thiazolidinedione, on Osteoblastogenesis and Bone Mineral Density in Mice.
10.3803/EnM.2017.32.3.389
- Author:
Kyoung Min KIM
1
;
Hyun Jin JIN
;
Seo Yeon LEE
;
Hyo Jin MAENG
;
Gha Young LEE
;
Tae Jung OH
;
Sung Hee CHOI
;
Hak Chul JANG
;
Soo LIM
Author Information
1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. limsoo@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Lobeglitazone;
Thiazolidinediones;
Bone and bones;
Bone density;
Osteoblasts
- MeSH:
Adipogenesis;
Alkaline Phosphatase;
Animals;
Biology;
Bone and Bones;
Bone Density*;
Diabetes Mellitus, Type 2;
Femur;
Gene Expression;
Humans;
In Vitro Techniques;
Infant;
Mice*;
Osteoblasts;
Osteocalcin;
Peroxisomes;
RNA, Messenger;
Thiazolidinediones;
Transcription Factors
- From:Endocrinology and Metabolism
2017;32(3):389-395
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Bone strength is impaired in patients with type 2 diabetes mellitus despite an increase in bone mineral density (BMD). Thiazolidinedione (TZD), a peroxisome proliferator activated receptor γ agonist, promotes adipogenesis, and suppresses osteoblastogenesis. Therefore, its use is associated with an increased risk of fracture. The aim of this study was to examine the in vitro and in vivo effects of lobeglitazone, a new TZD, on bone. METHODS: MC3T3E1 and C3H10T1/2 cells were cultured in osteogenic medium and exposed to lobeglitazone (0.1 or 1 µM), rosiglitazone (0.4 µM), or pioglitazone (1 µM) for 10 to 14 days. Alkaline phosphatase (ALP) activity, Alizarin red staining, and osteoblast marker gene expression were analyzed. For in vivo experiments, 6-month-old C57BL/6 mice were treated with vehicle, one of two doses of lobeglitazone, rosiglitazone, or pioglitazone. BMD was assessed using a PIXImus2 instrument at the baseline and after 12 weeks of treatment. RESULTS: As expected, in vitro experiments showed that ALP activity was suppressed and the mRNA expression of osteoblast marker genes RUNX2 (runt-related transcription factor 2) and osteocalcin was significantly attenuated after rosiglitazone treatment. By contrast, lobeglitazone at either dose did not inhibit these variables. Rosiglitazone-treated mice showed significantly accelerated bone loss for the whole bone and femur, but BMD did not differ significantly between the lobeglitazone-treated and vehicle-treated mice. CONCLUSION: These findings suggest that lobeglitazone has no detrimental effects on osteoblast biology and might not induce side effects in the skeletal system.
