Orexin-A Reverse Bone Mass Loss Induced by Chronic Intermittent Hypoxia Through OX1R-Nrf2/HIF-1α Pathway

References

• Lu Y, Liu Y, Li Y. Comparison of natural estrogens and synthetic derivative on genioglossus function and estrogen receptors expression in rats with chronic intermittent hypoxia. J Steroid Biochem Mol Biol. 2014;140:71–79.
   PubMed Web of Science ®Google Scholar
• Morselli LL, Guyon A, Spiegel K. Sleep and metabolic function. Pflugers Arch. 2012;463(1):139–160. doi:10.1007/s00424-011-1053-z
   PubMed Web of Science ®Google Scholar
• Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest. 2012;141(6):1601–1610. doi:10.1378/chest.11-2214
   PubMed Web of Science ®Google Scholar
• Kalogeris T, Baines CP, Krenz M, et al. Ischemia/Reperfusion. Compr Physiol. 2016;7(1):113–170. doi:10.1002/cphy.c160006
   PubMed Web of Science ®Google Scholar
• Wang W, Gu H, Li W, et al. SRC-3 knockout attenuates myocardial injury induced by chronic intermittent hypoxia in mice. Oxid Med Cell Longev. 2021;2021:6372430.
   PubMed Web of Science ®Google Scholar
• Tamisier R, Pépin JL, Rémy J, et al. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011;37(1):119–128. doi:10.1183/09031936.00204209
   PubMed Web of Science ®Google Scholar
• Swanson CM, Shea SA, Stone KL, et al. Obstructive sleep apnea and metabolic bone disease: insights into the relationship between bone and sleep. J Bone Miner Res. 2015;30(2):199–211. doi:10.1002/jbmr.2446
   PubMed Web of Science ®Google Scholar
• Hamada S, Ikezoe K, Hirai T, et al. Evaluation of bone mineral density by computed tomography in patients with obstructive sleep apnea. J Clin Sleep Med. 2016;12(1):25–34. doi:10.5664/jcsm.5386
   PubMed Web of Science ®Google Scholar
• Zhuang Y, Yan Y, Yang X, et al. Osteoporosis in a rat model co-exposed to cigarette smoke and intermittent hypoxia. Int J Chron Obstruct Pulmon Dis. 2020;15:2817–2825.
   PubMed Web of Science ®Google Scholar
• Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–342. doi:10.1038/nature01658
   PubMed Web of Science ®Google Scholar
• Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(5):1 page following 696. doi:10.1016/S0092-8674(00)80949-6
   Web of Science ®Google Scholar
• Nixon JP, Mavanji V, Butterick TA, et al. Sleep disorders, obesity, and aging: the role of orexin. Ageing Res Rev. 2015;20:63–73.
   PubMed Web of Science ®Google Scholar
• Han X, Zhou J, Peng W. Orexins facilitates osteogenic differentiation of MC3T3-E1 cells. IUBMB Life. 2018;70(7):633–641. doi:10.1002/iub.1757
   PubMed Web of Science ®Google Scholar
• Wei W, Motoike T, Krzeszinski JY, et al. Orexin regulates bone remodeling via a dominant positive central action and a subordinate negative peripheral action. Cell Metab. 2014;19(6):927–940. doi:10.1016/j.cmet.2014.03.016
   PubMed Web of Science ®Google Scholar
• Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437(7063):1257–1263. doi:10.1038/nature04284
   PubMed Web of Science ®Google Scholar
• Li L, Ren F, Qi C, et al. Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea. Respir Res. 2018;19(1):28. doi:10.1186/s12931-018-0727-x
   PubMed Web of Science ®Google Scholar
• Kang HS, Kwon HY, Kim IK, et al. Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer. Sci Rep. 2020;10(1):1854. doi:10.1038/s41598-020-58906-7
   PubMed Web of Science ®Google Scholar
• Brent MB. A review of the skeletal effects of exposure to high altitude and potential mechanisms for hypobaric hypoxia-induced bone loss. Bone. 2022;154:116258.
   PubMed Web of Science ®Google Scholar
• Drager J, Harvey EJ, Barralet J. Hypoxia signalling manipulation for bone regeneration. Expert Rev Mol Med. 2015;17:e6.
   PubMed Web of Science ®Google Scholar
• Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–732. doi:10.1038/nrc1187
   PubMed Web of Science ®Google Scholar
• Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323–328. doi:10.1038/nature13145
   PubMed Web of Science ®Google Scholar
• Tonelli C, Chio IIC, Tuveson DA. Transcriptional regulation by Nrf2. Antioxid Redox Signal. 2018;29(17):1727–1745. doi:10.1089/ars.2017.7342
   PubMed Web of Science ®Google Scholar
• Sánchez-de-Diego C, Pedrazza L, Pimenta-Lopes C, et al. NRF2 function in osteocytes is required for bone homeostasis and drives osteocytic gene expression. Redox Biol. 2021;40(17):101845. doi:10.1016/j.redox.2020.101845
   PubMed Web of Science ®Google Scholar
• Sun YX, Li L, Corry KA, et al. Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven bone formation. Bone. 2015;74(1):1–9. doi:10.1016/j.bone.2014.12.066
   PubMed Web of Science ®Google Scholar
• Lin G, Huang J, Chen Q, et al. miR-146a-5p mediates intermittent hypoxia-induced injury in H9c2 cells by targeting XIAP. Oxid Med Cell Longev. 2019;2019(6581217):1–11. doi:10.1155/2019/6581217
   Web of Science ®Google Scholar
• Shin SK, Song SE, Oh JU, et al. Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance. Pflugers Arch. 2019;471(11–12):1407–1418. doi:10.1007/s00424-019-02318-8
   PubMed Web of Science ®Google Scholar
• Lee EJ, Heo W, Kim JY, et al. Alteration of inflammatory mediators in the upper and lower airways under chronic intermittent hypoxia: preliminary animal study. Mediators Inflamm. 2017;2017(4327237):1–7. doi:10.1155/2017/4327237
   Web of Science ®Google Scholar
• Li W, Zhao J, Sun W, et al. Osteocytes promote osteoclastogenesis via autophagy-mediated RANKL secretion under mechanical compressive force. Arch Biochem Biophys. 2020;694(108594):108594. doi:10.1016/j.abb.2020.108594
   PubMed Web of Science ®Google Scholar
• Yang JX, Xie P, Li YS, et al. Osteoclast-derived miR-23a-5p-containing exosomes inhibit osteogenic differentiation by regulating Runx2. Cell Signal. 2020;70:109504. doi:10.1016/j.cellsig.2019.109504
   PubMed Web of Science ®Google Scholar
• Adeghate E, Lotfy M, D’Souza C, et al. Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin. Diabetes Metab Res Rev. 2020;36(3):e3229. doi:10.1002/dmrr.3229
   PubMed Web of Science ®Google Scholar
• Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009;373(9657):82–93. doi:10.1016/S0140-6736(08)61622-0
   PubMed Web of Science ®Google Scholar
• Ismail K, Roberts K, Manning P, et al. OSA and pulmonary hypertension: time for a new look. Chest. 2015;147(3):847–861. doi:10.1378/chest.14-0614
   PubMed Web of Science ®Google Scholar
• Vilovic M, Dogas Z, Ticinovic Kurir T, et al. Bone metabolism parameters and inactive matrix Gla protein in patients with obstructive sleep apnea. Sleep. 2020;43(3). doi:10.1093/sleep/zsz243.
   PubMed Web of Science ®Google Scholar
• Fletcher EC, Lesske J, Qian W, et al. Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats. Hypertension. 1992;19(6 Pt 1):555–561. doi:10.1161/01.HYP.19.6.555
   PubMed Web of Science ®Google Scholar
• Guo H, Zhang Y, Han T, et al. Chronic intermittent hypoxia aggravates skeletal muscle aging by down-regulating Klc1/grx1 expression via Wnt/β-catenin pathway. Arch Gerontol Geriatr. 2021;96(3):104460. doi:10.1016/j.archger.2021.104460
   PubMed Web of Science ®Google Scholar
• Arnett TR. Acidosis, hypoxia and bone. Arch Biochem Biophys. 2010;503(1):103–109. doi:10.1016/j.abb.2010.07.021
   PubMed Web of Science ®Google Scholar
• Yellowley CE, Genetos DC. Hypoxia signaling in the skeleton: implications for bone health. Curr Osteoporos Rep. 2019;17(1):26–35. doi:10.1007/s11914-019-00500-6
   PubMed Web of Science ®Google Scholar
• McAlpine CS, Kiss MG, Rattik S, et al. Sleep modulates haematopoiesis and protects against atherosclerosis. Nature. 2019;566(7744):383–387. doi:10.1038/s41586-019-0948-2
   PubMed Web of Science ®Google Scholar
• Hirai T, Tanaka K, Togari A. α1-adrenergic receptor signaling in osteoblasts regulates clock genes and bone morphogenetic protein 4 expression through up-regulation of the transcriptional factor nuclear factor IL-3 (Nfil3)/E4 promoter-binding protein 4 (E4BP4). J Biol Chem. 2014;289(24):17174–17183. doi:10.1074/jbc.M113.546135
   PubMed Web of Science ®Google Scholar
• Tysoe O. Melatonin prevents diabetes mellitus-induced bone loss. Nat Rev Endocrinol. 2021;17(12):707. doi:10.1038/s41574-021-00581-3
   PubMed Web of Science ®Google Scholar
• Yadav VK, Oury F, Suda N, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138(5):976–989. doi:10.1016/j.cell.2009.06.051
   PubMed Web of Science ®Google Scholar
• Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019;393(10169):364–376. doi:10.1016/S0140-6736(18)32112-3
   PubMed Web of Science ®Google Scholar
• Zhang L, Jin L, Guo J, et al. Chronic intermittent hypobaric hypoxia enhances bone fracture healing. Front Endocrinol. 2020;11:582670.
   PubMed Web of Science ®Google Scholar
• Bromer FD, Brent MB, Pedersen M, et al. The effect of normobaric intermittent hypoxia therapy on bone in normal and disuse osteopenic mice. High Alt Med Biol. 2021;22(2):225–234. doi:10.1089/ham.2020.0164
   PubMed Web of Science ®Google Scholar
• Navarrete-Opazo A, Mitchell GS. Therapeutic potential of intermittent hypoxia: a matter of dose. Am J Physiol Regul Integr Comp Physiol. 2014;307(10):R1181–97. doi:10.1152/ajpregu.00208.2014
   PubMed Web of Science ®Google Scholar
• Zhu J, Tang Y, Wu Q, et al. HIF-1α facilitates osteocyte-mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro. J Cell Physiol. 2019;234(11):21182–21192. doi:10.1002/jcp.28721
   PubMed Web of Science ®Google Scholar
• Lacey DC, Simmons PJ, Graves SE, et al. Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. Osteoarthritis Cartilage. 2009;17(6):735–742. doi:10.1016/j.joca.2008.11.011
   PubMed Web of Science ®Google Scholar
• Sánchez-de-la-Torre M, Barceló A, Piérola J, et al. Plasma levels of neuropeptides and metabolic hormones, and sleepiness in obstructive sleep apnea. Respir Med. 2011;105(12):1954–1960. doi:10.1016/j.rmed.2011.08.014
   PubMed Web of Science ®Google Scholar
• Aksu K, Firat Güven S, Aksu F, et al. Obstructive sleep apnoea, cigarette smoking and plasma orexin-A in a sleep clinic cohort. J Int Med Res. 2009;37(2):331–340. doi:10.1177/147323000903700207
   PubMed Web of Science ®Google Scholar
• Busquets X, Barbé F, Barceló A, et al. Decreased plasma levels of orexin-A in sleep apnea. Respiration. 2004;71(6):575–579. doi:10.1159/000081757
   PubMed Web of Science ®Google Scholar
• Sakurai S, Nishijima T, Takahashi S, et al. Low plasma orexin-A levels were improved by continuous positive airway pressure treatment in patients with severe obstructive sleep apnea-hypopnea syndrome. Chest. 2005;127(3):731–737. doi:10.1378/chest.127.3.731
   PubMed Web of Science ®Google Scholar
• Zhu J, Tang S, Zhao D, et al. Orexin A improves the cognitive impairment induced by chronic intermittent hypoxia in mice. Brain Res Bull. 2021;173(203):203–210. doi:10.1016/j.brainresbull.2021.05.022
   PubMed Web of Science ®Google Scholar
• Xu D, Kong T, Zhang S, et al. Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway. Cell Signal. 2021;79(109839):109839. doi:10.1016/j.cellsig.2020.109839
   PubMed Web of Science ®Google Scholar
• Park CK, Lee Y, Kim KH, et al. Nrf2 is a novel regulator of bone acquisition. Bone. 2014;63(36):36–46. doi:10.1016/j.bone.2014.01.025
   PubMed Web of Science ®Google Scholar
• Fonseca H, Moreira-Gonçalves D, Esteves JL, et al. Voluntary exercise has long-term in vivo protective effects on osteocyte viability and bone strength following ovariectomy. Calcif Tissue Int. 2011;88(6):443–454. doi:10.1007/s00223-011-9476-2
   PubMed Web of Science ®Google Scholar
• Sun YX, Xu AH, Yang Y, et al. Role of Nrf2 in bone metabolism. J Biomed Sci. 2015;22(101):1–7.
   PubMedGoogle Scholar
• Pellegrini GG, Morales CC, Wallace TC, et al. Avenanthramides prevent osteoblast and osteocyte apoptosis and induce osteoclast apoptosis in vitro in an Nrf2-independent manner. Nutrients. 2016;8(7):423. doi:10.3390/nu8070423
   PubMed Web of Science ®Google Scholar
• Chen X, Zhu X, Wei A, et al. Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis. Bone Res. 2021;9(1):15. doi:10.1038/s41413-020-00128-8
   PubMed Web of Science ®Google Scholar
• Meijer TW, Kaanders JH, Span PN, et al. Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clin Cancer Res. 2012;18(20):5585–5594. doi:10.1158/1078-0432.CCR-12-0858
   PubMed Web of Science ®Google Scholar
• Wan X, Liu Y, Zhao Y, et al. Orexin A affects HepG2 human hepatocellular carcinoma cells glucose metabolism via HIF-1α-dependent and -independent mechanism. PLoS One. 2017;12(9):e0184213. doi:10.1371/journal.pone.0184213
   PubMed Web of Science ®Google Scholar
• Sikder D, Kodadek T. The neurohormone orexin stimulates hypoxia-inducible factor-1 activity. Genes Dev. 2007;21(22):2995–3005. doi:10.1101/gad.1584307
   PubMed Web of Science ®Google Scholar