21 August 2017 : Laboratory Research
Parathyroid Hormone (PTH) Induces Autophagy to Protect Osteocyte Cell Survival from Dexamethasone DamageLiang Zhu12BCE, Jifei Chen1DF, Jing Zhang1CDF, Changan Guo1DF, Wenshuai Fan1BCF, Yi-ming Wang1BE, Zuoqin Yan1ADG*
Med Sci Monit 2017; 23:4034-4040
BACKGROUND: Glucocorticoids (GC) have direct adverse effects on osteocytes, the most abundant bone cell type, and play an important role in osteonecrosis of the femoral head (ONFH). Teriparatide has been reported to be an effective treatment for ONFH. However, the underlying mechanism is unclear.
MATERIAL AND METHODS: An osteocyte cell line, MLO-Y4, was used under various doses of dexamethasone (Dex) with or without rhPTH (1-34). Cell viability, autophagy, and apoptosis markers and osteocyte characteristic mRNAs were investigated to better understand this phenomenon.
RESULTS: Induction of apoptosis by Dex was increased in a time- and dose-dependent manner in MLO-Y4 cells. Autophagy markers (LC3-II and Beclin-1) were increased at the low dose of Dex (10^–7 or 10^–6 M) and decreased at the high dose (10^–5 M). In MOL-Y4 cells, rhPTH (1-34) was shown to be protective against Dex-induced apoptosis. The upregulation of LC3-II and Beclin-1 and decreased level of Caspase-3 was observed in the rhPTH (1-34)-treated group compared with the Dex-only-treated group. Furthermore, the changes induced by Dex in osteocytes, such as increased SOST, RANKL, and DMP-1 mRNA level and decreased Destrin mRNA level, were reversed by rhPTH (1-34). A similar result was found in osteocyte-specific proteins sclerostin expression encoded by SOST mRNA, which acted as a bone formation inhibitor.
CONCLUSIONS: The self-activation of autophagy may be a protective mechanism against apoptosis induced by Dex. The protection effect of rhPTH (1-34) for GC-induced ONFH thus results, at least in part, from enhanced autophagy.
Keywords: Dexamethasone Isonicotinate, Osteocytes, osteonecrosis, Parathyroid Hormone
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