PMID- 31108107 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20200526 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 376 DP - 2019 Aug 1 TI - Tanshinone prevents alveolar bone loss in ovariectomized osteoporosis rats by up-regulating phosphoglycerate dehydrogenase. PG - 9-16 LID - S0041-008X(19)30185-1 [pii] LID - 10.1016/j.taap.2019.05.014 [doi] AB - Osteoporosis is manifested by reduced bone mass. Tanshinone has been shown to affect osteoclast differentiation, but its role in osteoporosis remains less clear. This study aimed to investigate the effects and molecular mechanisms of tanshinone on osteoporosis. Osteoporosis was induced by bilateral ovariectomy (OVX) in adult female rats treated with or without tanshinone. Trabecular bone structure was assessed by micro-computed tomography (micro-CT). Bone marrow stromal cells (BMSCs) were isolated for analysis of stemness and senescence. mRNA levels of age related genes were examined and the role of the gene that was upregulated by tanshinone treatment was suppressed to determine its involvement in tanshinone mediated effects. Finally, the mechanism underlying tanshinone induced gene upregulation was explored. We found that tanshinone treatment restored alveolar bone structure in OVX rats as well as the stemness and senescence status of BMSCs isolated from OVX rats. Tanshinone upregulated Phgdh mRNA levels and inhibition of phosphoglycerate dehydrogenase Phgdh, the protein encoded by the Phgdh gene, abolished the effects of tanshinone on BMSC stemness and senescence. Finally, we found that OVX lead to hypermethylation of the promoter region of Phgdh which was suppressed by tanshinone treatment. Our study shows that tanshinone potently suppress OVX induced osteoporosis and BMSC senescence through upregulation of PHGDH. CI - Copyright (c) 2019. Published by Elsevier Inc. FAU - Wang, Luyao AU - Wang L AD - The Center of Stomatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Cheng, Liangxing AU - Cheng L AD - Editorial Department of Journal of Basic and Clinical Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Zhang, Baixia AU - Zhang B AD - The Center of Stomatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Wang, Nan AU - Wang N AD - Department of Emergency Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: alpha19820607@163.com. FAU - Wang, Feng AU - Wang F AD - Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai 201306, China. Electronic address: fengwang4@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190517 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Abietanes) RN - 0 (Drugs, Chinese Herbal) RN - 0 (RNA, Messenger) RN - 03UUH3J385 (tanshinone) RN - EC 1.1.1.95 (Phosphoglycerate Dehydrogenase) SB - IM MH - Abietanes/*administration & dosage MH - Alveolar Bone Loss/*prevention & control MH - Animals MH - Cells, Cultured MH - Cellular Senescence/drug effects MH - DNA Methylation/drug effects MH - Drugs, Chinese Herbal MH - Female MH - Mesenchymal Stem Cells/chemistry/drug effects/physiology MH - Osteoporosis/diet therapy/etiology/*physiopathology MH - *Ovariectomy MH - Phosphoglycerate Dehydrogenase/*genetics MH - Promoter Regions, Genetic/drug effects MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Up-Regulation/*drug effects OTO - NOTNLM OT - Aging OT - Alveolar bone loss OT - Osteoporosis OT - Phosphoglycerate dehydrogenase (PHGDH) OT - Tanshinone EDAT- 2019/05/21 06:00 MHDA- 2020/05/27 06:00 CRDT- 2019/05/21 06:00 PHST- 2019/05/11 00:00 [received] PHST- 2019/05/16 00:00 [accepted] PHST- 2019/05/21 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2019/05/21 06:00 [entrez] AID - S0041-008X(19)30185-1 [pii] AID - 10.1016/j.taap.2019.05.014 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2019 Aug 1;376:9-16. doi: 10.1016/j.taap.2019.05.014. Epub 2019 May 17.