PMID- 33324039 OWN - NLM STAT- MEDLINE DCOM- 20210921 LR - 20220419 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 14 DP - 2020 TI - Neohesperidin Ameliorates Steroid-Induced Osteonecrosis of the Femoral Head by Inhibiting the Histone Modification of lncRNA HOTAIR. PG - 5419-5430 LID - 10.2147/DDDT.S255276 [doi] AB - BACKGROUND: Neohesperidin (NH) and lncRNA HOTAIR (HOTAIR) could regulate osteoclastic and osteogenic differentiation. This study aimed to explore whether HOTAIR-mediated osteogenic differentiation was regulated by NH. METHODS: Steroid-induced osteonecrosis of the femoral head (SONFH) mice model was established. Histopathological changes in mouse osteonecrosis tissues were detected by hematoxylin-eosin staining. Bone marrow stromal cells (BMSCs) were isolated from healthy mice bone marrow samples by Ficoll density gradient and identified by flow cytometry. After treating the BMSCs with NH and dexamethasone or transfecting with HOTAIR overexpression plasmids and siHOTAIR, histone modification of HOTAIR, the cell viability, osteogenic differentiation, and adipogenic differentiation were detected by chromatin immunoprecipitation, MTT, Alizarin Red and Oil Red O staining, respectively. The expressions of HOTAIR and differentiation-related factors in the BMSCs were detected by RT-qPCR and Western blot. RESULTS: HOTAIR was highly expressed in SONFH model mice. NH ameliorated histopathological changes in the model mice, but the effect was reversed by overexpressed HOTAIR. NH increased viability of BMSCs and the H3K27me3 occupancy of HOTAIR, but decreased the expression and the H3K4me3 occupancy of HOTAIR. HOTAIR expression was down-regulated in BMSCs after osteogenic differentiation but was up-regulated after adipogenic differentiation. HOTAIR overexpression inhibited osteogenic differentiation and the expressions of RUNX2, OCN, and ALP, but increased adipogenic differentiation and the expressions of LPL and PPARr in BMSCs; moreover, the opposite results were observed in siHOTAIR. CONCLUSION: NH ameliorated SONFH by inhibiting the histone modifications of HOTAIR. CI - (c) 2020 Yuan et al. FAU - Yuan, Shuai AU - Yuan S AD - Department of Joint Surgery and Sports Medicine, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China. FAU - Zhang, Chuanxin AU - Zhang C AD - Department of Joint Surgery and Sports Medicine, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China. FAU - Zhu, Yunli AU - Zhu Y AD - Department of Joint Surgery and Sports Medicine, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China. FAU - Wang, Bo AU - Wang B AD - Department of Joint Surgery and Sports Medicine, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China. LA - eng PT - Journal Article DEP - 20201207 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (HOTAIR long non-coding RNA, mouse) RN - 0 (Histones) RN - 0 (RNA, Long Noncoding) RN - 0 (Steroids) RN - E750O06Y6O (Hesperidin) RN - OA5C88H3L0 (neohesperidin) SB - IM MH - Animals MH - Femur Head/*drug effects/metabolism/pathology MH - Hesperidin/*analogs & derivatives/pharmacology MH - Histones/*antagonists & inhibitors/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Osteogenesis/*drug effects MH - RNA, Long Noncoding/genetics/*metabolism MH - Steroids/antagonists & inhibitors/pharmacology PMC - PMC7733036 OTO - NOTNLM OT - HOTAIR OT - adipogenic OT - bone marrow stromal cells OT - neohesperidin OT - osteogenesis COIS- Non-financial competing interests. The authors report no other potential conflicts of interest for this work. EDAT- 2020/12/17 06:00 MHDA- 2021/09/22 06:00 PMCR- 2020/12/07 CRDT- 2020/12/16 05:35 PHST- 2020/03/24 00:00 [received] PHST- 2020/10/08 00:00 [accepted] PHST- 2020/12/16 05:35 [entrez] PHST- 2020/12/17 06:00 [pubmed] PHST- 2021/09/22 06:00 [medline] PHST- 2020/12/07 00:00 [pmc-release] AID - 255276 [pii] AID - 10.2147/DDDT.S255276 [doi] PST - epublish SO - Drug Des Devel Ther. 2020 Dec 7;14:5419-5430. doi: 10.2147/DDDT.S255276. eCollection 2020.