High glucose promotes mineralization via bone morphogenetic protein 4-Smad signals in early stage of osteoblast differen
- PDF / 944,286 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 74 Downloads / 176 Views
ORIGINAL ARTICLE
High glucose promotes mineralization via bone morphogenetic protein 4‑Smad signals in early stage of osteoblast differentiation Ayumu Takeno1,2 · Ippei Kanazawa1,3,4 · Ken‑ichiro Tanaka1,4,5 · Masakazu Notsu1 · Keizo Kanasaki1 · Takamasa Oono2 · Yoshihiro Ogawa2 · Toshitsugu Sugimoto1,6 Received: 3 March 2020 / Accepted: 24 August 2020 © The Japan Diabetes Society 2020
Abstract Diabetes mellitus is associated with bone fragility. Although osteoblast maturation is disturbed in patients with diabetes mellitus, the involvement of high glucose (HG) in different stages of osteoblast maturation is unclear. We used MC3T3-E1 cells, a murine osteoblastic cell line. The cells were incubated in high glucose medium (16.5 and 27.5 mM) with three different time courses: throughout 21 days, only first 7 days (early stage) and only last 7 days (late stage). Mineralization assay showed that HG throughout 21 days increased mineralization compared with control (5.5 mM). In the time course experiment, HG increased mRNA expression of Alp, osteocalcin (Ocn), runt-related transcription factor 2 and osterix on days 3 and 5. By contrast, long-term treatment with HG (14 and 21 days) decreased expression of these osteoblastic markers. HG only during early stage enhanced mineralization, while HG only during late stage had no effects. HG increased the expression of bone morphogenetic protein (BMP) 4 and enhanced phosphorylation of Smad1/5/8. Treatment with a BMP receptor antagonist LDN193189 prevented the HG-induced mineralization during early stage of osteoblast differentiation, indicating that HG in the early stage promotes mineralization by BMP4. In conclusion, the study demonstrates that continuous HG treatment might enhance early osteoblast differentiation but disturbs osteoblast maturation, and that BMP-4-Smad signal might be involved in the HG-induced differentiation and mineralization of osteoblasts. Keywords High glucose · MC3T3-E1 cell · Osteoblast · Bone morphogenetic protein 4 · Smad
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13340-020-00463-5) contains supplementary material, which is available to authorized users. * Ippei Kanazawa [email protected]‑u.ac.jp 1
Internal Medicine 1, Shimane University Faculty of Medicine, 89‑1, Enya‑cho, Izumo, Shimane 693‑8501, Japan
2
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3‑1‑1, Maidashi, Higashi‑ku, Fukuoka 812‑8582, Japan
3
Kanazawa Diabetes and Osteoporosis Clinic, 990‑2, Enya‑cho, Izumo, Shimane 693‑0021, Japan
4
Shimane BMD Laboratory, 990‑2, Enya‑cho, Izumo, Shimane 693‑0021, Japan
5
Department of Internal Medicine, Matsue Memorial Hospital, 3‑4‑1, Kaminogi, Matsue, Shimane 690‑0015, Japan
6
Eikokai Ono Hospital, 973, Tenjin‑cho, Ono, Hyogo, Japan
Accumulating evidence has shown that diabetes mellitus (DM) is associated with bone fragility [1–3]. The underlying mechanism of DM-induced bone fragility seems to be
Data Loading...
