Osteoking improves OP rat by enhancing HSP90‑β expression

Sun,Yan; Chen,Ran; Zhu,Di; Shen,Zhi‑Qiang; Zhao,Hong‑Bin; Lee,Wen‑Hui

doi:10.3892/ijmm.2020.4529

Osteoking improves OP rat by enhancing HSP90‑β expression

Authors:
- Yan Sun
- Ran Chen
- Di Zhu
- Zhi‑Qiang Shen
- Hong‑Bin Zhao
- Wen‑Hui Lee
View Affiliations

Affiliations: Pharmaceutical College and Key Laboratory of Pharmacology for Natural Products of Yunnan Province, Kunming Medical University, Kunming, Yunnan 650500, P.R. China, The Clinical Laboratory Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China, The Emergency Department, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650032, P.R. China, Key Laboratory of Bio‑active Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, 650032, P.R. China
Published online on: March 6, 2020 https://doi.org/10.3892/ijmm.2020.4529
Pages: 1543-1553
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoporosis (OP) is a chronic bone disease that affects individuals worldwide. Osteoporosis is primarily asymptomatic, and patients with OP suffer from pain, inconvenience, economic pressure and osteoporotic fracture (OPF). Osteoking, a Traditional Chinese Medicine compound that originates from the Yi ethnic group, has been used for a number of years to treat fractures. In our previous study, osteoking exhibited therapeutic effects on rats with OPF by promoting calcium deposition. Based on bioinformatics and network pharmacology analyses of a component‑target‑disease database, heat shock protein HSP 90‑β (HSP90‑β), also known as HSP90‑β, was identified to be a key target of osteoking in OP. High HSP90‑β expression levels were observed in osteoporotic rats and rat bone mesenchymal stem cells (rBMSCs) following osteoking treatment. After 12 weeks of administration in vivo, there was increased bone mineral density (BMD) (P<0.05), increased bone alkaline phosphatase (P<0.05), and improved bone microstructure in the osteoking group compared with those of the negative control group. In vitro, increased calcium deposition in rBMSCs was observed after 4 weeks of osteoking treatment. These results suggest that the mechanisms of osteoking are closely associated with HSP90‑β and activate the bone morphogenetic protein (BMP) signalling pathway, primarily through BMP‑2. Osteoking treatment improves OP in rats by enhancing HSP90‑β expression.

View Figures

View References

1	Dunnewind T, Dvortsin EP, Smeets HM, Konijn RM, Bos JHJ, de Boer PT, van den Bergh JP and Postma MJ: Economic consequences and potentially preventable costs related to osteoporosis in the Netherlands. Value Health. 20:762–768. 2017. View Article : Google Scholar : PubMed/NCBI
2	Ensrud KE and Crandall CJ: Osteoporosis. Ann Intern Med. 168:306–307. 2018. View Article : Google Scholar : PubMed/NCBI
3	McClung MR: Denosumab for the treatment of osteoporosis. Osteoporos Sarcopenia. 3:8–17. 2017. View Article : Google Scholar : PubMed/NCBI
4	Fukumoto S and Matsumoto T: Recent advances in the management of osteoporosis. F1000Res. 6:6252017. View Article : Google Scholar : PubMed/NCBI
5	Qaseem A, Forciea MA, McLean RM and Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: A clinical practice guideline update from the American college of physicians. Ann Intern Med. 166:818–839. 2017. View Article : Google Scholar : PubMed/NCBI
6	Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B and Kanis JA: Osteoporosis in the European Union: Medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 8:1362013. View Article : Google Scholar : PubMed/NCBI
7	Ramírez J, Nieto-González JC, Curbelo Rodríguez R, Castañeda S and Carmona L: Prevalence and risk factors for osteoporosis and fractures in axial spondyloarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 48:44–52. 2018. View Article : Google Scholar : PubMed/NCBI
8	Tawaratsumida H, Setoguchi T, Arishima Y, Ohtsubo H, Akimoto M, Ishidou Y, Nagano S, Taketomi E, Sunahara N and Komiya S: Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs. BMC Res Notes. 10:7652017. View Article : Google Scholar : PubMed/NCBI
9	Minisola S, Cipriani C, Occhiuto M and Pepe J: New anabolic therapies for osteoporosis. Intern Emerg Med. 12:915–921. 2017. View Article : Google Scholar : PubMed/NCBI
10	Rossini M, Adami S, Bertoldo F, Diacinti D, Gatti D, Giannini S, Giusti A, Malavolta N, Minisola S, Osella G, et al: Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo. 68:1–39. 2016. View Article : Google Scholar : PubMed/NCBI
11	Kanis JA, Cooper C, Rizzoli R and Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 30:3–44. 2019. View Article : Google Scholar
12	Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause. 17:25–54; quiz 55–26. 2010. View Article : Google Scholar : PubMed/NCBI
13	Dai L, Wu H, Yu S, Zhao H, Xue L, Xu M, Shen Z and Hu M: Effects of OsteoKing on osteoporotic rabbits. Mol Med Rep. 12:1066–1074. 2015. View Article : Google Scholar : PubMed/NCBI
14	Fan L, Ma J, Chen Y and Chen X: Antioxidant and antimicrobial phenolic compounds from Setaria viridis. Chem Nat Compounds. 50:433–437. 2014. View Article : Google Scholar
15	Hu M, Zhao HB, Qian CY, et al: Ultrastructural evaluation of the SANFH rabbit animal models intervened by Osteoking. Chin J Tradit Chin Med Pharm. 26:486–489. 2011.(In Chinese).
16	Zhao HB, Hu M and Liang HS: Experimental study on osteoking in promoting gene expression of core binding factor alpha 1 in necrotic femoral head of rabbits. Zhongguo Zhong Xi Yi Jie He Za Zhi. 26:1003–1006. 2006.(In Chinese). PubMed/NCBI
17	Zhao H, Hu M, Wang W and Li L: Effects of the VEGF gene expressions of Osteoking in the treatment of femoral head necrosis. China J Orthop Traumatol. 20:757–759. 2007.
18	Zhao HB, Hu M, Zheng HY, Liang HS and Zhu XS: Clinical study on effect of Osteoking in preventing postoperational deep venous thrombosis in patients with intertrochanteric fracture. Chin J Integr Med. 22:297–299. 2005.
19	Yan S: The effect of Osteoking on ovariectomized female rat model of Osteoporosis in Chinese. Chin J Osteoporosis. 12:21–24. 2016.
20	Hu M, Zhao HB, Wang B, Liang HS, Zhang CQ, Zheng HY and Zhao XL: Clinical observation on promoting effect of henggu gushang union agent on post-operational healing of Gosselin’s fracture. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2:160–161. 2005.(In Chinese).
21	Hasan S, Bonde BK, Buchan NS and Hall MD: Network analysis has diverse roles in drug discovery. Drug Discov Today. 17:869–874. 2012. View Article : Google Scholar : PubMed/NCBI
22	Keiser MJ, Setola V, Irwin JJ, Laggner C, Abbas AI, Hufeisen SJ, Jensen NH, Kuijer MB, Matos RC, Tran TB, et al: Predicting new molecular targets for known drugs. Nature. 462:175–181. 2009. View Article : Google Scholar : PubMed/NCBI
23	Qin D, Zhang H, Zhang H, Sun T, Zhao H and Lee WH: Anti-osteoporosis effects of osteoking via reducing reactive oxygen species. J Ethnopharmacol. 244:1120452019. View Article : Google Scholar : PubMed/NCBI
24	Jones-Bolin S: Guidelines for the care and use of laboratory animals in biomedical research. Curr Protoc Pharmacol. Appendix 4: Appendix 4B. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ahlquist RP: Experimental methods in pharmacology. J Pharm Sci. 59:7282010. View Article : Google Scholar
26	Morgan SL and Prater GL: Quality in dual-energy X-ray absorptiometry scans. Bone. 104:13–28. 2017. View Article : Google Scholar : PubMed/NCBI
27	Clough E and Barrett T: The gene expression omnibus database. Methods Mol Biol. 1418:93–110. 2016. View Article : Google Scholar : PubMed/NCBI
28	Gage GJ, Kipke DR and Shain W: Whole animal perfusion fixation for rodents. J Vis Exp. 35642012.PubMed/NCBI
29	Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ and Müller R: Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 25:1468–1486. 2010. View Article : Google Scholar : PubMed/NCBI
30	The UniProt Consortium. The universal protein knowledgebase. Nucleic Acids Res. 45:D158–D169. 2017. View Article : Google Scholar
31	NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 46:D8–D13. 2018. View Article : Google Scholar :
32	Kibbe WA: OligoCalc: An online oligonucleotide properties calculator. Nucleic Acids Res. 35(Web Server issue): W43–W46. 2007. View Article : Google Scholar : PubMed/NCBI
33	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
34	Guo XL, Liu LZ, Wang QQ, Liang JY, Lee WH, Xiang Y, Li SA and Zhang Y: Endogenous pore-forming protein complex targets acidic glycosphingolipids in lipid rafts to initiate endolysosome regulation. Commun Biol. 2:592019. View Article : Google Scholar : PubMed/NCBI
35	Zuehlke AD, Moses MA and Neckers L: Heat shock protein 90: Its inhibition and function. Philos Trans R Soc Lond B Biol Sci. 373:201605272018. View Article : Google Scholar
36	Yan X, Hui Y, Hua Y, Huang L, Wang L, Peng F, Tang C, Liu D, Song J and Wang F: EG-VEGF silencing inhibits cell proliferation and promotes cell apoptosis in pancreatic carcinoma via PI3K/AKT/mTOR signaling pathway. Biomed Pharmacother. 109:762–769. 2019. View Article : Google Scholar
37	Saryeddine L, Zibara K, Kassem N, Badran B and El-Zein N: EGF-induced VEGF exerts a PI3K-dependent positive feedback on ERK and AKT through VEGFR2 in hematological in vitro models. PLoS One. 11:e01658762016. View Article : Google Scholar : PubMed/NCBI
38	Yasui H, Hideshima T, Ikeda H, Jin J, Ocio EM, Kiziltepe T, Okawa Y, Vallet S, Podar K, Ishitsuka K, et al: BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth. Br J Haematol. 136:414–423. 2007. View Article : Google Scholar
39	Khong T and Spencer A: Targeting HSP90 induces apoptosis and inhibits critical survival and proliferation pathways in multiple myeloma. Mol Cancer Ther. 10:1909–1917. 2011. View Article : Google Scholar : PubMed/NCBI
40	Miyasaka M, Nakata H, Hao J, Kim YK, Kasugai S and Kuroda S: Low-intensity pulsed ultrasound stimulation enhances heat-shock protein 90 and mineralized nodule formation in mouse calvaria-derived osteoblasts. Tissue Eng Part A. 21:2829–2839. 2015. View Article : Google Scholar : PubMed/NCBI
41	Tash JS, Chakrasali R, Jakkaraj SR, Hughes J, Smith SK, Hornbaker K, Heckert LL, Ozturk SB, Hadden MK, Kinzy TG, et al: Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and stimulates Il1a transcription in rat Sertoli cells. Biol Reprod. 78:1139–1152. 2008. View Article : Google Scholar : PubMed/NCBI
42	Yao Y, Watson AD, Ji S and Bostrom KI: Heat shock protein 70 enhances vascular bone morphogenetic protein-4 signaling by binding matrix Gla protein. Circ Res. 105:575–584. 2009. View Article : Google Scholar : PubMed/NCBI
43	Zhang Z, Ma Y, Guo S, He Y, Bai G and Zhang W: Low-intensity pulsed ultrasound stimulation facilitates in vitro osteogenic differentiation of human adipose-derived stem cells via up-regulation of heat shock protein (HSP)70, HSP90, and bone morphogenetic protein (BMP) signaling pathway. Biosci Rep. 38:BSR201800872018. View Article : Google Scholar :
44	Chung E, Sampson AC and Rylander MN: Influence of heating and cyclic tension on the induction of heat shock proteins and bone-related proteins by MC3T3-E1 cells. Biomed Res Int. 2014:354260. 2014. View Article : Google Scholar
45	Graner MW: HSP90 and immune modulation in cancer. Adv Cancer Res. 129:191–224. 2016. View Article : Google Scholar : PubMed/NCBI
46	Vázquez-Carrera M: HSP90 inhibitors as a future therapeutic strategy in diabetes-driven atherosclerosis. Clin Investig Arterioscler. 29:67–68. 2017.(In English, Spanish). PubMed/NCBI
47	Yu C, Dai L, Ma Z, Zhao H, Yuan Y, Zhang Y, Bao P, Su Y, Ma D, Liu C, et al: Effect of Osteoking on the osteogenic and adipogenic differentiation potential of rat bone marrow mesenchymal stem cells in vitro. BMC Complement Altern Med. 19:362019. View Article : Google Scholar : PubMed/NCBI
48	Huang K, Wu G, Zou J and Peng S: Combination therapy with BMP-2 and psoralen enhances fracture healing in ovariectomized mice. Exp Ther Med. 16:1655–1662. 2018.PubMed/NCBI
49	Griffith JF, Wang YX, Zhou H, Kwong WH, Wong WT, Sun YL, Huang Y, Yeung DK, Qin L and Ahuja AT: Reduced bone perfusion in osteoporosis: Likely causes in an ovariectomy rat model. Radiology. 254:739–746. 2010. View Article : Google Scholar : PubMed/NCBI
50	Ding WG, Wei ZX and Liu JB: Reduced local blood supply to the tibial metaphysis is associated with ovariectomy-induced osteoporosis in mice. Connect Tissue Res. 52:25–29. 2011. View Article : Google Scholar
51	Peng J, Lai ZG, Fang ZL, Xing S, Hui K, Hao C, Jin Q, Qi Z, Shen WJ, Dong QN, et al: Dimethyloxalylglycine prevents bone loss in ovariectomized C57BL/6J mice through enhanced angiogenesis and osteogenesis. PLoS One. 9:e1127442014. View Article : Google Scholar : PubMed/NCBI