Bencaosome [16:0 Lyso PA+XLGB28-sRNA] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice.

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      Publisher: Published for the International Union of Biochemistry and Molecular Biology by Taylor & Francis Country of Publication: England NLM ID: 100888706 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-6551 (Electronic) Linking ISSN: 15216543 NLM ISO Abbreviation: IUBMB Life Subsets: MEDLINE
    • Publication Information:
      Original Publication: London ; Philadelphia, PA : Published for the International Union of Biochemistry and Molecular Biology by Taylor & Francis, c1999-
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    • Abstract:
      Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28-sRNA targeting TNFSF11 exerted a significant anti-osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28-sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28-sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.
      (© 2024 International Union of Biochemistry and Molecular Biology.)
    • References:
      Armas LA, Recker RR. Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am. 2012;41(3):475–486. https://doi.org/10.1016/j.ecl.2012.04.006.
      NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785–795. https://doi.org/10.1001/jama.285.6.785.
      Srivastava M, Deal C. Osteoporosis in elderly: prevention and treatment. Clin Geriatr Med. 2002;18(3):529–555. https://doi.org/10.1016/s0749-0690(02)00022-8.
      Coughlan T, Dockery F. Osteoporosis and fracture risk in older people. Clin Med (Lond). 2014;14(2):187–191. https://doi.org/10.7861/clinmedicine.14-2-187.
      Ensrud KE, Crandall CJ. Osteoporosis. Ann Intern Med. 2017;167(3):Itc17–itc32. https://doi.org/10.7326/aitc201708010.
      Vestergaard Kvist A, Faruque J, Vallejo‐Yagüe E, Weiler S, Winter EM, Burden AM. Cardiovascular safety profile of romosozumab: a pharmacovigilance analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS). J Clin Med. 2021;10(8):1660. https://doi.org/10.3390/jcm10081660.
      Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of postmenopausal osteoporosis‐2020 update. Endocr Pract. 2020;26(Suppl 1):1–46. https://doi.org/10.4158/gl-2020-0524suppl.
      Guañabens N, Moro‐Álvarez MJ, Casado E, Blanch‐Rubió J, Gómez‐Alonso C, Díaz‐Guerra GM, et al. The next step after anti‐osteoporotic drug discontinuation: an up‐to‐date review of sequential treatment. Endocrine. 2019;64(3):441–455. https://doi.org/10.1007/s12020-019-01919-8.
      Wang P, Perche F, Logeart‐Avramoglou D, Pichon C. RNA‐based therapy for osteogenesis. Int J Pharm. 2019;569:118594. https://doi.org/10.1016/j.ijpharm.2019.118594.
      Chen X, Rechavi O. Plant and animal small RNA communications between cells and organisms. Nat Rev Mol Cell Biol. 2022;23(3):185–203. https://doi.org/10.1038/s41580-021-00425-y.
      Li F, Yang Y, Zhu P, Chen W, Qi D, Shi X, et al. Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3‐E1 cells. Fitoterapia. 2012;83(8):1443–1450. https://doi.org/10.1016/j.fitote.2012.08.008.
      Du J, Liang Z, Xu J, Zhao Y, Li X, Zhang Y, et al. Plant‐derived phosphocholine facilitates cellular uptake of anti‐pulmonary fibrotic HJT‐sRNA‐m7. Sci China Life Sci. 2019;62(3):309–320. https://doi.org/10.1007/s11427-017-9026-7.
      Tang K, Wang Z, Zhao Y, Li X, Jiang Z, Mei S, et al. Oral administration of herbal oligonucleotide XKC‐sRNA‐h3 prevents angiotensin II‐induced hypertension in mice. Sci China Life Sci. 2023;66(10):2370–2379.
      Cao Yinghao LY, Na S, Xinyi D, Yixin D, Song M, Xingyu D, et al. A comprehensive analysis of the Bencao (herbal) small RNA atlas reveals novel RNA therapeutics for treating human diseases. Sci China Life Sci. 2023;66(7):1589–1599.
      Zhao Dandan QY, Jiaqi L, Tang Kegong L, Shuaiyao LZ, Yexuan L, Cong Z, et al. Orally administered BZL‐sRNA‐20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice. SCIENCE CHINA Life Sciences; 2022.
      Li X, Liang Z, Du J, Wang Z, Mei S, Li Z, et al. Herbal decoctosome is a novel form of medicine. Sci China Life Sci. 2019;62(3):333–348. https://doi.org/10.1007/s11427-018-9508-0.
      Zhu HM, Qin L, Garnero P, Genant HK, Zhang G, Dai K, et al. The first multicenter and randomized clinical trial of herbal Fufang for treatment of postmenopausal osteoporosis. Osteoporos Int. 2012;23(4):1317–1327. https://doi.org/10.1007/s00198-011-1577-2.
      Cheng Y, Liu Y, Wang H, Li J, Ren J, Zhu L, et al. A 26‐week repeated dose toxicity study of Xian‐ling‐gu‐bao in Sprague‐Dawley rats. J Ethnopharmacol. 2013;145(1):85–93. https://doi.org/10.1016/j.jep.2012.09.055.
      Wang X, He Y, Guo B, Tsang MC, Tu F, Dai Y, et al. In vivo screening for anti‐osteoporotic fraction from extract of herbal formula Xianlinggubao in ovariectomized mice. PLoS One. 2015;10(2):e0118184. https://doi.org/10.1371/journal.pone.0118184.
      Chen SH, Wang XL, Zheng LZ, Dai Y, Zhang JY, Guo BL, et al. Comparative study of two types of herbal capsules with different Epimedium species for the prevention of ovariectomised‐induced osteoporosis in rats. J Orthop Translat. 2016;4:14–27. https://doi.org/10.1016/j.jot.2015.07.001.
      Wu H, Zhong Q, Wang J, Wang M, Fang F, Xia Z, et al. Beneficial effects and toxicity studies of Xian‐ling‐gu‐bao on bone metabolism in Ovariectomized rats. Front Pharmacol. 2017;8:273. https://doi.org/10.3389/fphar.2017.00273.
      Wu X, Sun S, Wu X, Sun Z. Multitech‐based study on medicinal material basis and action mechanism of herbal formula Xian‐Ling‐Gu‐Bao capsule in treatment of osteoarthritis. Evid Based Complement Alternat Med. 2022;2022:6986372. https://doi.org/10.1155/2022/6986372.
      Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006. https://doi.org/10.1002/0471143030.cb0322s30.
      Li X, Zhang J, Kong X, Xerenbek T, Mamet T. Yak (Bos grunniens) milk improves bone mass and microarchitecture in mice with osteoporosis. J Dairy Sci. 2022;105(10):7878–7890. https://doi.org/10.3168/jds.2022-21880.
      Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov. 2017;16(1):19–34. https://doi.org/10.1038/nrd.2016.230.
      Kulkarni JA, Witzigmann D, Thomson SB, Chen S, Leavitt BR, Cullis PR, et al. The current landscape of nucleic acid therapeutics. Nat Nanotechnol. 2021;16(6):630–643. https://doi.org/10.1038/s41565-021-00898-0.
      Crooke ST, Witztum JL, Bennett CF, Baker BF. RNA‐targeted therapeutics. Cell Metab. 2018;27(4):714–739. https://doi.org/10.1016/j.cmet.2018.03.004.
      Yu AM, Choi YH, Tu MJ. RNA drugs and RNA targets for small molecules: principles, progress, and challenges. Pharmacol Rev. 2020;72(4):862–898. https://doi.org/10.1124/pr.120.019554.
      Roberts TC, Langer R, Wood MJA. Advances in oligonucleotide drug delivery. Nat Rev Drug Discov. 2020;19(10):673–694. https://doi.org/10.1038/s41573-020-0075-7.
      An J, Yang H, Zhang Q, Liu C, Zhao J, Zhang L, et al. Natural products for treatment of osteoporosis: the effects and mechanisms on promoting osteoblast‐mediated bone formation. Life Sci. 2016;147:46–58. https://doi.org/10.1016/j.lfs.2016.01.024.
      Stein GS, Lian JB, Owen TA. Relationship of cell growth to the regulation of tissue‐specific gene expression during osteoblast differentiation. FASEB J. 1990;4(13):3111–3123. https://doi.org/10.1096/fasebj.4.13.2210157.
      Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, et al. Increased bone formation in osteocalcin‐deficient mice. Nature. 1996;382(6590):448–452. https://doi.org/10.1038/382448a0.
      Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger‐containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108(1):17–29. https://doi.org/10.1016/s0092-8674(01)00622-5.
      Hinoi E, Fujimori S, Wang L, Hojo H, Uno K, Yoneda Y. Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2‐dependent transcriptional activation. J Biol Chem. 2006;281(26):18015–18024. https://doi.org/10.1074/jbc.M600603200.
      McDonald MM, Khoo WH, Ng PY, Xiao Y, Zamerli J, Thatcher P, et al. Osteoclasts recycle via osteomorphs during RANKL‐stimulated bone resorption. Cell. 2021;184(5):1330–1347.e1313. https://doi.org/10.1016/j.cell.2021.02.002.
      Gao X, Wu Q, Zhang X, Tian J, Liang D, Min Y, et al. Salvianolate ameliorates osteopenia and improves bone quality in prednisone‐treated rheumatoid arthritis rats by regulating RANKL/RANK/OPG signaling. Front Pharmacol. 2021;12:710169. https://doi.org/10.3389/fphar.2021.710169.
      Cao X. RANKL‐RANK signaling regulates osteoblast differentiation and bone formation. Bone Res. 2018;6:35. https://doi.org/10.1038/s41413-018-0040-9.
      Sritharan S, Kannan TP, Norazmi MN, Nurul AA. The synergistic effects of IL‐6/IL‐17A promote osteogenic differentiation by improving OPG/RANKL ratio and adhesion of MC3T3‐E1 cells on hydroxyapatite. J Craniomaxillofac Surg. 2018;46(8):1361–1367. https://doi.org/10.1016/j.jcms.2018.05.002.
      Wu R, Li Q, Pei X, Hu K. Effects of brucine on the OPG/RANKL/RANK signaling pathway in MDA‐MB‐231 and MC3T3‐E1 cell coculture system. Evid Based Complement Alternat Med. 2017;2017:1693643. https://doi.org/10.1155/2017/1693643.
      Mai QG, Zhang ZM, Xu S, Lu M, Zhou RP, Zhao L, et al. Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem. 2011;112(10):2902–2909. https://doi.org/10.1002/jcb.23206.
    • Grant Information:
      2021-I2M-1-022 Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; BP0820029 Higher Education Discipline Innovation Project; 81788101 National Natural Science Foundation of China; 2060204 State Key Laboratory Special Fund; 2017PT31017 Fundamental Research Funds for Central Universities
    • Contributed Indexing:
      Keywords: RNA therapy; TNFSF11; Xianlinggubao; bone delivery; oligonucleotide drug; osteoporosis; small RNA; traditional Chinese medicine
    • Accession Number:
      0 (Drugs, Chinese Herbal)
      0 (Tnfsf11 protein, mouse)
      0 (Liposomes)
      0 (RANK Ligand)
    • Publication Date:
      Date Created: 20240716 Date Completed: 20241018 Latest Revision: 20241022
    • Publication Date:
      20241023
    • Accession Number:
      10.1002/iub.2857
    • Accession Number:
      39012196