Generic placeholder image

Current Drug Therapy

Author(s): Junyi He, Wenxuan Zeng, Xiaoyun Ye, Xiaoshuang Niu, Juan Liu* and Zhihui Chen*

DOI: 10.2174/0115748855342971240816120237

DownloadDownload PDF Flyer Cite As
Targeted Drug Delivery for Precision Mitochondrial Therapy in Osteoporosis: Therapeutic Strategies and Advances

Page: [76 - 94] Pages: 19

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Osteoporosis (OP) remains a significant global health challenge, marked by high prevalence and considerable economic burden, yet effective therapeutic options remain limited. Central to the pathogenesis of OP is mitochondrial dysfunction, which adversely impacts bone formation and resorption. This review provides an in-depth analysis of the complex relationship between mitochondrial function and OP, elucidating critical molecular mechanisms and identifying promising therapeutic agents. Among these, zoledronic acid and resveratrol stand out, demonstrating significant efficacy in enhancing mitochondrial functions and enhancing bone density in both preclinical models and clinical trials. Moreover, innovative drug delivery systems, such as mitochondrial-targeted nanodelivery systems and localized delivery methods, have been developed to ensure precise targeting and reduce systemic side effects, thereby enhancing bioavailability and therapeutic outcomes. By delving into these advancements, this review seeks to facilitate the translation of mitochondrial-targeted therapies from preclinical research to clinical application, ultimately advancing OP management and improving patient outcomes.

Keywords: Osteoporosis, mitochondrial dysfunction, mitochondrial-targeted drugs, drug delivery, nanoparticles, hydrogels, scaffolds.

Graphical Abstract

[1]
Kanis JA, Johnell O, Oden A, et al. Long-term risk of osteoporotic fracture in Malmö. Osteoporos Int 2000; 11(8): 669-74.
[http://dx.doi.org/10.1007/s001980070064] [PMID: 11095169]
[2]
Melton LJ, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL. Bone density and fracture risk in men. J Bone Miner Res 1998; 13(12): 1915-23.
[http://dx.doi.org/10.1359/jbmr.1998.13.12.1915] [PMID: 9844110]
[3]
Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis? J Bone Miner Res 1992; 7(9): 1005-10.
[http://dx.doi.org/10.1002/jbmr.5650070902] [PMID: 1414493]
[4]
Curtis EM, van der Velde R, Moon RJ, et al. Epidemiology of fractures in the United Kingdom 1988–2012: Variation with age, sex, geography, ethnicity and socioeconomic status. Bone 2016; 87: 19-26.
[http://dx.doi.org/10.1016/j.bone.2016.03.006] [PMID: 26968752]
[5]
Borgström F, Karlsson L, Ortsäter G, et al. Fragility fractures in Europe: burden, management and opportunities. Arch Osteoporos 2020; 15(1): 59.
[http://dx.doi.org/10.1007/s11657-020-0706-y] [PMID: 32306163]
[6]
Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, Afanador-Restrepo DF, Carcelén-Fraile MC, López-Ruiz E. Current status of the diagnosis and management of osteoporosis. Int J Mol Sci 2022; 23(16): 9465.
[http://dx.doi.org/10.3390/ijms23169465] [PMID: 36012730]
[7]
Kim J, Kim BY, Lee JS, et al. UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis. Nat Commun 2023; 14(1): 3668.
[http://dx.doi.org/10.1038/s41467-023-39448-8] [PMID: 37339951]
[8]
Zhang Y, Liu H, Zhang C, et al. Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese. Sci Rep 2015; 5(1): 16783.
[http://dx.doi.org/10.1038/srep16783] [PMID: 26568273]
[9]
Martemucci G, Portincasa P, Di Ciaula A, Mariano M, Centonze V, D’Alessandro AG. Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview. Mech Ageing Dev 2022; 206: 111707.
[http://dx.doi.org/10.1016/j.mad.2022.111707] [PMID: 35839856]
[10]
Chandra A, Rajawat J. Skeletal aging and osteoporosis: mechanisms and therapeutics. Int J Mol Sci 2021; 22(7): 3553.
[http://dx.doi.org/10.3390/ijms22073553] [PMID: 33805567]
[11]
Chen W, Zhao H, Li Y. Mitochondrial dynamics in health and disease: mechanisms and potential targets. Signal Transduct Target Ther 2023; 8(1): 333.
[http://dx.doi.org/10.1038/s41392-023-01547-9] [PMID: 37669960]
[12]
Liu J, Gao Z, Liu X. Mitochondrial dysfunction and therapeutic perspectives in osteoporosis. Front Endocrinol (Lausanne) 2024; 15: 1325317.
[http://dx.doi.org/10.3389/fendo.2024.1325317] [PMID: 38370357]
[13]
Li S, Kim MJ, Lee SH, et al. Metallothionein 3 promotes osteoblast differentiation in C2C12 cells via reduction of oxidative stress. Int J Mol Sci 2021; 22(9): 4312.
[http://dx.doi.org/10.3390/ijms22094312] [PMID: 33919218]
[14]
Srinivasan S, Koenigstein A, Joseph J, et al. Role of mitochondrial reactive oxygen species in osteoclast differentiation. Ann N Y Acad Sci 2010; 1192(1): 245-52.
[http://dx.doi.org/10.1111/j.1749-6632.2009.05377.x] [PMID: 20392243]
[15]
Wang Y, Zhao X, Lotz M, Terkeltaub R, Liu-Bryan R. Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but reversible via peroxisome proliferator-activated receptor γ coactivator 1α. Arthritis Rheumatol 2015; 67(8): 2141-53.
[http://dx.doi.org/10.1002/art.39182] [PMID: 25940958]
[16]
Gan X, Huang S, Yu Q, Yu H, Yan SS. Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction. Biochem Biophys Res Commun 2015; 468(4): 719-25.
[http://dx.doi.org/10.1016/j.bbrc.2015.11.022] [PMID: 26577411]
[17]
Cai WJ, Chen Y, Shi LX, et al. AKT-GSK3β signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage contributing to osteoblast apoptosis: preventative effects of hydroxytyrosol. Oxid Med Cell Longev 2019; 2019: 1-20.
[http://dx.doi.org/10.1155/2019/4101738] [PMID: 31281574]
[18]
Zhang F, Peng W, Zhang J, et al. P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head. Cell Death Dis 2020; 11(1): 42.
[http://dx.doi.org/10.1038/s41419-020-2238-1] [PMID: 31959744]
[19]
Yang X, Jiang T, Wang Y, Guo L. The role and mechanism of SIRT1 in resveratrol-regulated osteoblast autophagy in osteoporosis rats. Sci Rep 2019; 9(1): 18424.
[http://dx.doi.org/10.1038/s41598-019-44766-3] [PMID: 31804494]
[20]
Chen H, Han Z, Wang Y, et al. Targeting ferroptosis in bone-related diseases: facts and perspectives. J Inflamm Res 2023; 16: 4661-77.
[http://dx.doi.org/10.2147/JIR.S432111] [PMID: 37872954]
[21]
Catheline SE, Kaiser E, Eliseev RA. Mitochondrial genetics and function as determinants of bone phenotype and aging. Curr Osteoporos Rep 2023; 21(5): 540-51.
[http://dx.doi.org/10.1007/s11914-023-00816-4] [PMID: 37542684]
[22]
Ren L, Chen X, Chen X, Li J, Cheng B, Xia J. Mitochondrial dynamics: fission and fusion in fate determination of mesenchymal stem cells. Front Cell Dev Biol 2020; 8: 580070.
[http://dx.doi.org/10.3389/fcell.2020.580070] [PMID: 33178694]
[23]
Yan C, Shi Y, Yuan L, et al. Mitochondrial quality control and its role in osteoporosis. Front Endocrinol (Lausanne) 2023; 14: 1077058.
[http://dx.doi.org/10.3389/fendo.2023.1077058] [PMID: 36793284]
[24]
Li Q, Huang Y. Mitochondrial targeted strategies and their application for cancer and other diseases treatment. J Pharm Investig 2020; 50(3): 271-93.
[http://dx.doi.org/10.1007/s40005-020-00481-0]
[25]
Bețiu AM, Noveanu L, Hâncu IM, et al. Mitochondrial effects of common cardiovascular medications: the good, the bad and the mixed. Int J Mol Sci 2022; 23(21): 13653.
[http://dx.doi.org/10.3390/ijms232113653] [PMID: 36362438]
[26]
Chindamo G, Sapino S, Peira E, Chirio D, Gonzalez MC, Gallarate M. Bone diseases: current approach and future perspectives in drug delivery systems for bone targeted therapeutics. Nanomaterials (Basel) 2020; 10(5): 875.
[http://dx.doi.org/10.3390/nano10050875] [PMID: 32370009]
[27]
Arai M, Shibata Y, Pugdee K, Abiko Y, Ogata Y. Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3‐E1 cells. IUBMB Life 2007; 59(1): 27-33.
[http://dx.doi.org/10.1080/15216540601156188] [PMID: 17365177]
[28]
Chen M, Wang D, Li M, et al. Nanocatalytic biofunctional MOF coating on titanium implants promotes osteoporotic bone regeneration through cooperative pro-osteoblastogenesis MSC reprogramming. ACS Nano 2022; 16(9): 15397-412.
[http://dx.doi.org/10.1021/acsnano.2c07200] [PMID: 36106984]
[29]
Jin W, Zhu X, Yao F, et al. Cytoprotective effect of Fufang Lurong Jiangu capsule against hydrogen peroxide-induced oxidative stress in bone marrow stromal cell-derived osteoblasts through the Nrf2/HO-1 signaling pathway. Biomed Pharmacother 2020; 121: 109676.
[http://dx.doi.org/10.1016/j.biopha.2019.109676] [PMID: 31810119]
[30]
Zhang X, Zhang D, Zhao H, et al. gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice. Mol Med Rep 2024; 30(2): 133.
[http://dx.doi.org/10.3892/mmr.2024.13257] [PMID: 38818814]
[31]
Fraser JHE, Helfrich MH, Wallace HM, Ralston SH. Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae. Bone 1996; 19(3): 223-6.
[http://dx.doi.org/10.1016/8756-3282(96)00177-9] [PMID: 8873962]
[32]
Ishii K, Fumoto T, Iwai K, et al. Coordination of PGC-1β and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med 2009; 15(3): 259-66.
[http://dx.doi.org/10.1038/nm.1910] [PMID: 19252502]
[33]
Kim JM, Jeong D, Kang HK, Jung SY, Kang SS, Min BM. Osteoclast precursors display dynamic metabolic shifts toward accelerated glucose metabolism at an early stage of RANKL-stimulated osteoclast differentiation. Cell Physiol Biochem 2007; 20(6): 935-46.
[http://dx.doi.org/10.1159/000110454] [PMID: 17982276]
[34]
Richardson KK, Ling W, Krager K, et al. Ionizing radiation activates mitochondrial function in osteoclasts and causes bone loss in young adult male mice. Int J Mol Sci 2022; 23(2): 675.
[http://dx.doi.org/10.3390/ijms23020675] [PMID: 35054859]
[35]
Ho L, Wang L, Roth TM, et al. Sirtuin-3 promotes adipogenesis, osteoclastogenesis, and bone loss in aging male mice. Endocrinology 2017; 158(9): 2741-53.
[http://dx.doi.org/10.1210/en.2016-1739] [PMID: 28911171]
[36]
Kim HN, Han L, Iyer S, et al. Sirtuin1 suppresses osteoclastogenesis by seacetylating FoxOs. Mol Endocrinol 2015; 29(10): 1498-509.
[http://dx.doi.org/10.1210/me.2015-1133] [PMID: 26287518]
[37]
Feng J, Liu S, Ma S, et al. Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway. Acta Biochim Biophys Sin (Shanghai) 2014; 46(12): 1024-33.
[http://dx.doi.org/10.1093/abbs/gmu103] [PMID: 25377437]
[38]
Qu B, Gong K, Yang H, et al. SIRT1 suppresses high glucose and palmitate-induced osteoclast differentiation via deacetylating p66Shc. Mol Cell Endocrinol 2018; 474: 97-104.
[http://dx.doi.org/10.1016/j.mce.2018.02.015] [PMID: 29486220]
[39]
Klinge CM. Estrogens regulate life and death in mitochondria. J Bioenerg Biomembr 2017; 49(4): 307-24.
[http://dx.doi.org/10.1007/s10863-017-9704-1] [PMID: 28401437]
[40]
Popov LD. Mitochondrial biogenesis: An update. J Cell Mol Med 2020; 24(9): 4892-9.
[http://dx.doi.org/10.1111/jcmm.15194] [PMID: 32279443]
[41]
Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1. Cardiovasc Res 2008; 79(2): 208-17.
[http://dx.doi.org/10.1093/cvr/cvn098] [PMID: 18430751]
[42]
Buccoliero C, Dicarlo M, Pignataro P, et al. The Novel role of PGC1α in bone metabolism. Int J Mol Sci 2021; 22(9): 4670.
[http://dx.doi.org/10.3390/ijms22094670] [PMID: 33925111]
[43]
Colaianni G, Lippo L, Sanesi L, et al. Deletion of the transcription factor PGC-1α in mice negatively regulates bone mass. Calcif Tissue Int 2018; 103(6): 638-52.
[http://dx.doi.org/10.1007/s00223-018-0459-4] [PMID: 30094757]
[44]
Tang X, Ma S, Li Y, et al. Evaluating the activity of sodium butyrate to prevent osteoporosis in rats by promoting osteal GSK-3β/Nrf2 signaling and mitochondrial function. J Agric Food Chem 2020; 68(24): 6588-603.
[http://dx.doi.org/10.1021/acs.jafc.0c01820] [PMID: 32459091]
[45]
Zhang T, Chi Y, Kang Y, et al. Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC‐1α mediated attenuation of mitochondrial oxidative stress. J Cell Physiol 2019; 234(4): 5033-43.
[http://dx.doi.org/10.1002/jcp.27306] [PMID: 30187480]
[46]
Losón OC, Song Z, Chen H, Chan DC. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 2013; 24(5): 659-67.
[http://dx.doi.org/10.1091/mbc.e12-10-0721] [PMID: 23283981]
[47]
Song J, Herrmann JM, Becker T. Quality control of the mitochondrial proteome. Nat Rev Mol Cell Biol 2021; 22(1): 54-70.
[http://dx.doi.org/10.1038/s41580-020-00300-2] [PMID: 33093673]
[48]
Mao YX, Cai WJ, Sun XY, et al. RAGE-dependent mitochondria pathway: a novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products. Cell Death Dis 2018; 9(6): 674.
[http://dx.doi.org/10.1038/s41419-018-0718-3] [PMID: 29867140]
[49]
Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol 2018; 28(4): R170-85.
[http://dx.doi.org/10.1016/j.cub.2018.01.004] [PMID: 29462587]
[50]
Bader V, Winklhofer KF. PINK1 and Parkin: team players in stress-induced mitophagy. Biol Chem 2020; 401(6-7): 891-9.
[http://dx.doi.org/10.1515/hsz-2020-0135] [PMID: 32297878]
[51]
Guo Y, Jia X, Cui Y, et al. Sirt3-mediated mitophagy regulates AGEs-induced BMSCs senescence and senile osteoporosis. Redox Biol 2021; 41: 101915.
[http://dx.doi.org/10.1016/j.redox.2021.101915] [PMID: 33662874]
[52]
Chen L, Shi X, Weng SJ, et al. Vitamin K2 can rescue the dexamethasone-induced downregulation of osteoblast autophagy and mitophagy thereby restoring osteoblast function in vitro and in vivo. Front Pharmacol 2020; 11: 1209.
[http://dx.doi.org/10.3389/fphar.2020.01209] [PMID: 32848799]
[53]
Lee SY, An HJ, Kim JM, et al. PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis. Stem Cell Res Ther 2021; 12(1): 589.
[http://dx.doi.org/10.3390/cells11111724] [PMID: 35681421]
[54]
Sun X, Yang X, Zhao Y, Li Y, Guo L. Effects of 17β-estradiol on mitophagy in the murine MC3T3-E1 osteoblast cell line is mediated via G protein-coupled estrogen receptor and the ERK1/2 signaling pathway. Med Sci Monit 2018; 24: 903-11.
[http://dx.doi.org/10.12659/MSM.908705] [PMID: 29438359]
[55]
Ling W, Krager K, Richardson KK, et al. Mitochondrial Sirt3 contributes to the bone loss caused by aging or estrogen deficiency. JCI Insight 2021; 6(10): e146728.
[http://dx.doi.org/10.1172/jci.insight.146728] [PMID: 33878033]
[56]
Xie X, Hu L, Mi B, et al. Metformin alleviates bone loss in ovariectomized mice through inhibition of autophagy of osteoclast precursors mediated by E2F1. Cell Commun Signal 2022; 20(1): 165.
[http://dx.doi.org/10.1186/s12964-022-00966-5] [PMID: 36284303]
[57]
Kume S, Uzu T, Horiike K, et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 2010; 120(4): 1043-55.
[http://dx.doi.org/10.1172/JCI41376] [PMID: 20335657]
[58]
Tseng AHH, Shieh SS, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med 2013; 63: 222-34.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.002] [PMID: 23665396]
[59]
Wang Y, Li X, Zhou S, et al. MCU Inhibitor ruthenium red alleviates the osteoclastogenesis and ovariectomized osteoporosis via suppressing RANKL-induced ROS production and NFATc1 activation through P38 MAPK signaling pathway. Oxid Med Cell Longev 2022; 2022: 1-27.
[http://dx.doi.org/10.1155/2022/7727006] [PMID: 36148414]
[60]
Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev 2006; 38(4): 769-89.
[http://dx.doi.org/10.1080/03602530600971974] [PMID: 17145701]
[61]
Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 2019; 23: 101107.
[http://dx.doi.org/10.1016/j.redox.2019.101107] [PMID: 30692038]
[62]
Song X, Long D. Nrf2 and ferroptosis: a new research direction for neurodegenerative diseases. Front Neurosci 2020; 14: 267.
[http://dx.doi.org/10.3389/fnins.2020.00267] [PMID: 32372896]
[63]
Kim BJ, Lee SH, Koh JM, Kim GS. The association between higher serum ferritin level and lower bone mineral density is prominent in women ≥45 years of age (KNHANES 2008–2010). Osteoporos Int 2013; 24(10): 2627-37.
[http://dx.doi.org/10.1007/s00198-013-2363-0] [PMID: 23592044]
[64]
Kim BJ, Ahn SH, Bae SJ, et al. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: A 3-year retrospective longitudinal study. J Bone Miner Res 2012; 27(11): 2279-90.
[http://dx.doi.org/10.1002/jbmr.1692] [PMID: 22729843]
[65]
Xiao L, Andemariam B, Taxel P, et al. Loss of Bone in Sickle Cell Trait and Sickle Cell Disease Female Mice Is Associated With Reduced IGF-1 in Bone and Serum. Endocrinology 2016; 157(8): 3036-46.
[http://dx.doi.org/10.1210/en.2015-2001] [PMID: 27171384]
[66]
Valanezhad A, Odatsu T, Abe S, Watanabe I. Bone formation ability and cell viability enhancement of MC3T3-E1 cells by ferrostatin-1 a ferroptosis inhibitor of cancer cells. Int J Mol Sci 2021; 22(22): 12259.
[http://dx.doi.org/10.3390/ijms222212259] [PMID: 34830144]
[67]
Li Y, Bai B, Zhang Y. Bone abnormalities in young male rats with iron intervention and possible mechanisms. Chem Biol Interact 2018; 279: 21-6.
[http://dx.doi.org/10.1016/j.cbi.2017.11.005] [PMID: 29122540]
[68]
Xiao W, Beibei F, Guangsi S, et al. Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass. J Endocrinol 2015; 226(3): 121-34.
[http://dx.doi.org/10.1530/JOE-14-0657] [PMID: 26116610]
[69]
Ding G, Zhao J, Jiang D. Allicin inhibits oxidative stress-induced mitochondrial dysfunction and apoptosis by promoting PI3K/AKT and CREB/ERK signaling in osteoblast cells. Exp Ther Med 2016; 11(6): 2553-60.
[http://dx.doi.org/10.3892/etm.2016.3179] [PMID: 27284348]
[70]
Cao F, Yang K, Qiu S, et al. Metformin reverses oxidative stress‑induced mitochondrial dysfunction in pre‑osteoblasts via the EGFR/GSK‑3β/calcium pathway. Int J Mol Med 2023; 51(4): 36.
[http://dx.doi.org/10.3892/ijmm.2023.5239] [PMID: 36999607]
[71]
Zhao L, Wang Y, Wang Z, Xu Z, Zhang Q, Yin M. Effects of dietary resveratrol on excess-iron-induced bone loss via antioxidative character. J Nutr Biochem 2015; 26(11): 1174-82.
[http://dx.doi.org/10.1016/j.jnutbio.2015.05.009] [PMID: 26239832]
[72]
Pal S, Singh M, Porwal K, et al. Adiponectin receptors by increasing mitochondrial biogenesis and respiration promote osteoblast differentiation: Discovery of isovitexin as a new class of small molecule adiponectin receptor modulator with potential osteoanabolic function. Eur J Pharmacol 2021; 913: 174634.
[http://dx.doi.org/10.1016/j.ejphar.2021.174634] [PMID: 34785210]
[73]
Zhu FB, Wang JY, Zhang YL, et al. Curculigoside regulates proliferation, differentiation, and pro-inflammatory cytokines levels in dexamethasone-induced rat calvarial osteoblasts. Int J Clin Exp Med 2015; 8(8): 12337-46.
[PMID: 26550143]
[74]
Sarkar J, Das M, Howlader MSI, Prateeksha P, Barthels D, Das H. Epigallocatechin-3-gallate inhibits osteoclastic differentiation by modulating mitophagy and mitochondrial functions. Cell Death Dis 2022; 13(10): 908.
[http://dx.doi.org/10.1038/s41419-022-05343-1] [PMID: 36307395]
[75]
Li X, Lin H, Zhang X, et al. Notoginsenoside R1 attenuates oxidative stress‐induced osteoblast dysfunction through JNK signalling pathway. J Cell Mol Med 2021; 25(24): 11278-89.
[http://dx.doi.org/10.1111/jcmm.17054] [PMID: 34786818]
[76]
Park C, Lee H, Han MH, et al. Cytoprotective effects of fermented oyster extracts against oxidative stress-induced DNA damage and apoptosis through activation of the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblasts. EXCLI J 2020; 19: 1102-19.
[PMID: 33013267]
[77]
Mercken EM, Mitchell SJ, Martin-Montalvo A, et al. SRT 2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell 2014; 13(5): 787-96.
[http://dx.doi.org/10.1111/acel.12220] [PMID: 24931715]
[78]
Smith JJ. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo. BMC Sys Bio 2009; 3(1): 31.
[79]
Funk JA, Odejinmi S, Schnellmann RG. SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells. J Pharmacol Exp Ther 2010; 333(2): 593-601.
[http://dx.doi.org/10.1124/jpet.109.161992] [PMID: 20103585]
[80]
Li W, Jiang WS, Su YR, et al. PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products. Cell Death Dis 2023; 14(2): 88.
[http://dx.doi.org/10.1038/s41419-023-05595-5] [PMID: 36750550]
[81]
Maity J, Barthels D, Sarkar J, et al. Ferutinin induces osteoblast differentiation of DPSCs via induction of KLF2 and autophagy/mitophagy. Cell Death Dis 2022; 13(5): 452.
[http://dx.doi.org/10.1038/s41419-022-04903-9] [PMID: 35552354]
[82]
Chen T, Gao F, Luo D, et al. Cistanoside A promotes osteogenesis of primary osteoblasts by alleviating apoptosis and activating autophagy through involvement of the Wnt/β-catenin signal pathway. Ann Transl Med 2022; 10(2): 64-4.
[http://dx.doi.org/10.21037/atm-21-6742] [PMID: 35282110]
[83]
Jin ZH, Wang SF, Liao W. Zoledronic acid accelerates osteogenesis of bone marrow mesenchymal stem cells by attenuating oxidative stress via the SIRT3/SOD2 pathway and thus alleviates osteoporosis. Eur Rev Med Pharmacol Sci 2020; 24(4): 2095-101.
[PMID: 32141579]
[84]
Jing X, Du T, Chen K, et al. Icariin protects against iron overload‐induced bone loss via suppressing oxidative stress. J Cell Physiol 2019; 234(7): 10123-37.
[http://dx.doi.org/10.1002/jcp.27678] [PMID: 30387158]
[85]
Huang Q, Gao B, Wang L, et al. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. Toxicol Appl Pharmacol 2014; 280(3): 550-60.
[http://dx.doi.org/10.1016/j.taap.2014.08.004] [PMID: 25130202]
[86]
Zhang J. The osteoprotective effects of artemisinin compounds and the possible mechanisms associated with intracellular iron: A review of in vivo and in vitro studies. Environ Toxicol Pharmacol 2020; 76: 103358.
[http://dx.doi.org/10.1016/j.etap.2020.103358] [PMID: 32143118]
[87]
Ni S, Yuan Y, Qian Z, et al. Hypoxia inhibits RANKL-induced ferritinophagy and protects osteoclasts from ferroptosis. Free Radic Biol Med 2021; 169: 271-82.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.027] [PMID: 33895289]
[88]
Ding M, Cho E, Chen Z, Park SW, Lee TH. (S)-2-(Cyclobutylamino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)isonicotinamide attenuates RANKL-induced osteoclast differentiation by inhibiting NF-κB nuclear translocation. Int J Mol Sci 2023; 24(5): 4327.
[http://dx.doi.org/10.3390/ijms24054327] [PMID: 36901758]
[89]
Kim EN, Trang NM, Kang H, Kim KH, Jeong GS. Phytol suppresses osteoclast differentiation and oxidative stress through Nrf2/HO-1 regulation in RANKL-induced RAW264.7 cells. Cells 2022; 11(22): 3596.
[http://dx.doi.org/10.3390/cells11223596] [PMID: 36429027]
[90]
Che J, Yang J, Zhao B, et al. The effect of abnormal iron metabolism on osteoporosis. Biol Trace Elem Res 2020; 195(2): 353-65.
[http://dx.doi.org/10.1007/s12011-019-01867-4] [PMID: 31473898]
[91]
Chung J-H, Kim Y-S, Noh K, Lee Y-M, Chang S-W, Kim E-C. Deferoxamine promotes osteoblastic differentiation in human periodontal ligament cells via the nuclear factor erythroid 2‐related factor‐mediated antioxidant signaling pathway. J Periodontal Res 2014; 49(5): 563-73.
[http://dx.doi.org/10.1111/jre.12136] [PMID: 24111577]
[92]
Ma H, Wang X, Zhang W, et al. Melatonin suppresses ferroptosis induced by high glucose via activation of the Nrf2/HO-1 signaling pathway in Type 2 diabetic osteoporosis. Oxid Med Cell Longev 2020; 2020: 1-18.
[http://dx.doi.org/10.1155/2020/9067610] [PMID: 33343809]
[93]
Wang L, Lu WG, Shi J, et al. Anti-osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation. Mol Med Rep 2017; 16(6): 8307-14.
[http://dx.doi.org/10.3892/mmr.2017.7610] [PMID: 28983593]
[94]
Ballard A, Zeng R, Zarei A, et al. The tethering function of mitofusin2 controls osteoclast differentiation by modulating the Ca2+–NFATc1 axis. J Biol Chem 2020; 295(19): 6629-40.
[http://dx.doi.org/10.1074/jbc.RA119.012023] [PMID: 32165499]
[95]
Zhang W, Rong H, Liang J, et al. Chitosan modified with PAP as a promising delivery system for melatonin in the treatment of osteoporosis: targeting the divalent metal transporter 1. J Biol Eng 2024; 18(1): 27.
[http://dx.doi.org/10.1186/s13036-024-00422-7] [PMID: 38622739]
[96]
Chen L, Shi X, Xie J, et al. Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway. Free Radic Biol Med 2021; 163: 356-68.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.235] [PMID: 33385540]
[97]
Fazil M, Ali A, Baboota S, Sahni JK, Ali J. Exploring drug delivery systems for treating osteoporosis. Expert Opin Drug Deliv 2013; 10(8): 1123-36.
[http://dx.doi.org/10.1517/17425247.2013.785518] [PMID: 23537096]
[98]
Zheng Z, Yu C, Wei H. Injectable hydrogels as three-dimensional network reservoirs for osteoporosis treatment. Tissue Eng Part B Rev 2021; 27(5): 430-54.
[http://dx.doi.org/10.1089/ten.teb.2020.0168] [PMID: 33086984]
[99]
Wen C, Xu X, Zhang Y, Xia J, Liang Y, Xu L. Bone targeting nanoparticles for the treatment of osteoporosis. Int J Nanomedicine 2024; 19: 1363-83.
[http://dx.doi.org/10.2147/IJN.S444347] [PMID: 38371454]
[100]
Kotak DJ, Devarajan PV. Bone targeted delivery of salmon calcitonin hydroxyapatite nanoparticles for sublingual osteoporosis therapy (SLOT). Nanomedicine 2020; 24: 102153.
[http://dx.doi.org/10.1016/j.nano.2020.102153] [PMID: 31988038]
[101]
Shi S, Duan H, Ou X. Targeted delivery of anti-osteoporosis therapy: Bisphosphonate-modified nanosystems and composites. Biomed Pharmacother 2024; 175: 116699.
[http://dx.doi.org/10.1016/j.biopha.2024.116699] [PMID: 38705129]
[102]
Xi Y, Wang W, Ma L, et al. Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats. Drug Deliv 2022; 29(1): 2386-402.
[http://dx.doi.org/10.1080/10717544.2022.2086942] [PMID: 35869674]
[103]
Sun Y, Ye X, Cai M, et al. Osteoblast-targeting-peptide modified nanoparticle for siRNA/microRNA delivery. ACS Nano 2016; 10(6): 5759-68.
[http://dx.doi.org/10.1021/acsnano.5b07828] [PMID: 27176123]
[104]
Gao X, Li L, Cai X, Huang Q, Xiao J, Cheng Y. Targeting nanoparticles for diagnosis and therapy of bone tumors: Opportunities and challenges. Biomaterials 2021; 265: 120404.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120404] [PMID: 32987273]
[105]
Rosdah AA, Abbott BM, Langendorf CG, et al. A novel small molecule inhibitor of human Drp1. Sci Rep 2022; 12(1): 21531.
[http://dx.doi.org/10.1038/s41598-022-25464-z] [PMID: 36513726]
[106]
Cheng H, Chawla A, Yang Y, et al. Development of nanomaterials for bone-targeted drug delivery. Drug Discov Today 2017; 22(9): 1336-50.
[http://dx.doi.org/10.1016/j.drudis.2017.04.021] [PMID: 28487069]
[107]
Li L, Yu M, Li Y, et al. Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration. Bioact Mater 2021; 6(5): 1255-66.
[http://dx.doi.org/10.1016/j.bioactmat.2020.10.018] [PMID: 33210023]
[108]
Peng H, Qiu X, Cheng M, et al. Resveratrol-loaded nanoplatform RSV@DTPF promote alveolar bone regeneration in OVX rat through remodeling bone-immune microenvironment. Chem Eng J 2023; 476: 146615.
[http://dx.doi.org/10.1016/j.cej.2023.146615]
[109]
Liu S, Fu H, Lv Y, et al. α-Hemihydrate calcium sulfate/n-hydroxyapatite combined with metformin promotes osteogenesis in vitro and in vivo. Front Bioeng Biotechnol 2022; 10: 899157.
[http://dx.doi.org/10.3389/fbioe.2022.899157] [PMID: 36246380]
[110]
Zhang Q, Xin M, Yang S, et al. Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration. Mater Today Bio 2023; 20: 100623.
[http://dx.doi.org/10.1016/j.mtbio.2023.100623] [PMID: 37077506]
[111]
Liang H, Chen K, Xie J, et al. A bone-penetrating precise controllable drug release system enables localized treatment of osteoporotic fracture prevention via modulating osteoblast-osteoclast communication. Small 2023; 19(26): 2207195.
[http://dx.doi.org/10.1002/smll.202207195] [PMID: 36971278]
[112]
Shim HW, Kurian AG, Lee J, et al. Surface-engineered titanium with nanoceria to enhance soft tissue integration via reactive oxygen species modulation and nanotopographical sensing. ACS Appl Mater Interfaces 2024; 16(11): 13622-39.
[http://dx.doi.org/10.1021/acsami.4c02119] [PMID: 38466038]
[113]
Singh RK, Yoon DS, Mandakhbayar N, et al. Diabetic bone regeneration with nanoceria-tailored scaffolds by recapitulating cellular microenvironment: Activating integrin/TGF-β co-signaling of MSCs while relieving oxidative stress. Biomaterials 2022; 288: 121732.
[http://dx.doi.org/10.1016/j.biomaterials.2022.121732] [PMID: 36031457]
[114]
Kurian AG, Singh RK, Lee JH, Kim HW. Surface-Engineered Hybrid Gelatin Methacryloyl with Nanoceria as Reactive Oxygen Species Responsive Matrixes for Bone Therapeutics. ACS Appl Bio Mater 2022; 5(3): 1130-8.
[http://dx.doi.org/10.1021/acsabm.1c01189] [PMID: 35193358]
[115]
Park IS, Mahapatra C, Park JS, et al. Revascularization and limb salvage following critical limb ischemia by nanoceria-induced Ref-1/APE1-dependent angiogenesis. Biomaterials 2020; 242: 119919.
[http://dx.doi.org/10.1016/j.biomaterials.2020.119919] [PMID: 32146371]
[116]
Dayanandan AP, Cho WJ, Kang H, et al. Emerging nano-scale delivery systems for the treatment of osteoporosis. Biomater Res 2023; 27(1): 68.
[http://dx.doi.org/10.1186/s40824-023-00413-7] [PMID: 37443121]
[117]
Thang NH, Chien TB, Cuong DX. Polymer-based hydrogels applied in drug delivery: an overview. Gels 2023; 9(7): 523.
[http://dx.doi.org/10.3390/gels9070523] [PMID: 37504402]
[118]
Fang CH, Sun CK, Lin YW, et al. Metformin-incorporated gelatin/nano-hydroxyapatite scaffolds promotes bone regeneration in critical size rat alveolar bone defect model. Int J Mol Sci 2022; 23(1): 558.
[http://dx.doi.org/10.3390/ijms23010558] [PMID: 35008984]
[119]
Monavari M, Homaeigohar S, Fuentes-Chandía M, et al. 3D printing of alginate dialdehyde-gelatin (ADA-GEL) hydrogels incorporating phytotherapeutic icariin loaded mesoporous SiO2-CaO nanoparticles for bone tissue engineering. Mater Sci Eng C 2021; 131: 112470.
[http://dx.doi.org/10.1016/j.msec.2021.112470]
[120]
Mohammadzadeh M, Zarei M, Abbasi H, Webster TJ, Beheshtizadeh N. Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms. J Biol Eng 2024; 18(1): 29.
[http://dx.doi.org/10.1186/s13036-024-00425-4] [PMID: 38649969]
[121]
Jang JW, Min K-E, Kim C, Shin J, Lee J, Yi S. Review: scaffold characteristics, fabrication methods, and biomaterials for the bone tissue engineering. Int J Precis Eng Manuf 2023; 24(3): 511-29.
[http://dx.doi.org/10.1007/s12541-022-00755-7]
[122]
Lu Y, Li M, Li L, et al. High-activity chitosan/nano hydroxyapatite/zoledronic acid scaffolds for simultaneous tumor inhibition, bone repair and infection eradication. Mater Sci Eng C 2018; 82: 225-33.
[http://dx.doi.org/10.1016/j.msec.2017.08.043] [PMID: 29025652]
[123]
Zhang X, He J, Qiao L, et al. 3D printed PCLA scaffold with nano‐hydroxyapatite coating doped green tea EGCG promotes bone growth and inhibits multidrug‐resistant bacteria colonization. Cell Prolif 2022; 55(10): e13289.
[http://dx.doi.org/10.1111/cpr.13289] [PMID: 35791492]
[124]
Ran Z, Wang Y, Li J, et al. 3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair. Int J Bioprint 2023; 9(5): 769.
[http://dx.doi.org/10.18063/ijb.769] [PMID: 37457935]