Recovery from bone loss, diminished mineral density and strength in mice after treatment with steroidal and nonsteroidal anti-inflammatory drugs by injection of exosomes enriched with agomir miRNAs
Anti-inflammatory drugs impact on bones
DOI:
https://doi.org/10.20883/medical.379Keywords:
methylprednisolone, diclofenac, miRNA, bone, exercise, bone strenghtAbstract
The project “Recovery from bone loss, diminished mineral density and strength in mice after treatment with steroidal and nonsteroidal anti-inflammatory drugs by injection of exosomes enriched with agomir miRNAs” is an animal experiment project, and an attempt to apply small RNA strands to reverse the harmful effects of anti-inflammatory drugs. Patients chronically treated with an anti-inflammatory drug suffer from musculoskeletal side effects, including reversed mineralisation and disabled bone fracture healing. The aims of the study are to measure changes in bone mineral density and bone strength in mice treated with methylprednisolone or diclofenac in combination with treadmill exercise. The reversal of the negative effects of these drugs will be assayed using modified miRNA agomir. Bones obtained from the treated mice will be analysed using micro-CT, dynamic mechanical analysis (DMA), nanoindentation, Raman spectroscopy and gene expression. We expect to find specific miRNA counteracting the demineralisation of the mice bones caused by methylprednisolone or diclofenac.
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References
Siebler T, Robson H, Shalet SM, Williams GR. Dexamethasone inhibits and thyroid hormone promotes differentiation of mouse chondrogenic ATDC5 cells. Bone. 2002;31(4):457–64.
Hant FN, Bolster MB. Drugs that may harm bone: Mitigating the risk. Cleve Clin J Med. 2016;83(4):281–8.
Hartmann K, Koenen M, Schauer S, Wittig‑Blaich S, Ahmad M, Baschant U, et al. Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy. Physiol Rev. 2016;96(2):409–47.
Loi F, Cordova LA, Pajarinen J, Lin TH, Yao Z, Goodman SB. Inflammation, fracture and bone repair. Bone. 2016;86:119–30.
Kurmis AP, Kurmis TP, O'Brien JX, Dalen T. The effect of nonsteroidal anti‑inflammatory drug administration on acute phase fracture‑healing: a review. J Bone Joint Surg Am. 2012;94(9):815–23.
Zimmermann EA, Gludovatz B, Schaible E, Busse B, Ritchie RO. Fracture resistance of human cortical bone across multiple length‑scales at physiological strain rates. Biomaterials. 2014;35(21):5472–81.
Nair AK, Gautieri A, Chang SW, Buehler MJ. Molecular mechanics of mineralized collagen fibrils in bone. Nat Commun. 2013;4:1724.
Derry S, Conaghan P, Da Silva JA, Wiffen PJ, Moore RA. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2016;4:CD007400.
Moghadam‑Kia S, Werth VP. Prevention and treatment of systemic glucocorticoid side effects. Int J Dermatol. 2010;49(3):239–48.
Benkhadra K, Mohammed K, Al Nofal A, Carranza Leon BG, Alahdab F, Faubion S, et al. Menopausal Hormone Therapy and Mortality: A Systematic Review and Meta‑Analysis. J Clin Endocrinol Metab. 2015;100(11):4021–8.
Russo CR. The effects of exercise on bone. Basic concepts and implications for the prevention of fractures. Clin Cases Miner Bone Metab. 2009;6(3):223–8.
Santos L, Elliott‑Sale KJ, Sale C. Exercise and bone health across the lifespan. Biogerontology. 2017;18(6):931–946.
Jing D, Hao J, Shen Y, Tang G, Li ML, Huang SH, et al. The role of microRNAs in bone remodeling. Int J Oral Sci. 2015;7(3):131–43.
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Copyright (c) 2019 Tomasz P. Lehmann, Ewa Pruszyńska-Oszmałek, Paweł Kołodziejski, Magdalena Wojtków, Celina Pezowicz, Mirosław Szybowicz, Paweł P. Jagodziński, Marek Nowicki, Aleksandra Trzaskowska, Sławomir Mielcarek, Maciej Głowacki
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