Table Info

Table 3.

Role of nanoparticles in bone remodelling

NPs	Modifications	Therapeutic agents	Target (bone remodeling)	Experimental model	Inference	Reference
Liposomes	Gelatin methacryloyl-dopamine (GelMA-DOPA)	MT	Osteoblast	MC3T3-E1 (precursors osteoblast) and OVX mice model	MT promotes osteoblast differentiation and bone formation and has been effectively used to combat oxidative stress	[101]
PLGA	Nanodecoys	RAW cell membrane	Osteoclast	RAW 264.7 cells (preosteoclast) and OVX mouse model	Nanodecoys capable of scavenging RANKL and TNF-α produced by osteoclast cells and promote osteoblastogenesis	[103]
CS	Nano-HA (n-HA/resveratrol/chitosan)	Resveratrol	Osteoclast	RAW 264.7 cells and OVX rat model	CS microsphere implanted into bone defects in the osteoporotic rat femoral condyles, enhanced entochondrostosis and also possessed anti-inflammatory property to treat osteoporotic bone disorder	[106]
HA	IO NPs	miR-21 and miR-124	Osteoblast and osteoclast	MC3T3-E1, 4B12 cells and RAW 264.7 cells	nHAp/IO/miR-21/miR-124 improves metabolism of preosteoblasts and promotes osteogenesis, simultaneously decreasing differentiation of preosteoclasts	[107]
Mesoporous silica NPs		nanoceria	Osteoblast and osteoclast	MC3T3-E1 cells and RAW 264.7 cells	Ce-MSNs exhibited antioxidant capability and stimulated cell proliferation and osteogenic responses	[114]
Selenium NPs			Osteoblast	MC3T3-E1 cells	SeNPs in osteogenic differentiation in order to treat osteoporosis by regulating the oxidative stress	[118]
Gold NPs	EGCG	EGCG	Osteoclast	Bone marrow macrophages cells and in vivo LPS-induced calvarial bone erosion model	EGCG-GNPs exhibited anti-osteoclastogenesis by reducing the intracellular ROS generation and inhibited the MAPK pathway	[119]

NPs: nanoparticles; CS: chitosan; EGCG: epigallocatechin gallate; GNPs: gold nanoparticles

Declarations

Acknowledgment

LB is thankful to University Grants Commission-Senior research fellowship (UGC-SRF) for her fellowship. KN acknowledges Council of Scientific & Industrial Research-Senior research fellowship (CSIR-SRF) for her fellowship.

Author contributions

LB, KN and AKV conceived and wrote the manuscript. AKV edited the manuscript. All authors contributed to manuscript writing, revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

The work on siRNA was supported by the project grant “Small molecule functionalized biopolymeric nanoparticles encapsulating siRNA for targeted delivery to osteoblasts for managing bone disorders” (BT/PR 21645/NNT/28/1224/2017) from Department of Biotechnology, Government of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Eastell R, O’Neill TW, Hofbauer LC, Langdahl B, Reid IR, Gold DT, et al. Postmenopausal osteoporosis. Nat Rev Dis Primers. 2016;2:16069. [DOI] [PubMed]

Goulding A. Risk factors for fractures in normally active children and adolescents. Med Sport Sci. 2007;51:102–20. [DOI] [PubMed]

Zhao F, Guo L, Wang X, Zhang Y. Correlation of oxidative stress-related biomarkers with postmenopausal osteoporosis: a systematic review and meta-analysis. Arch Osteoporos. 2021;16:4. [DOI] [PubMed]

Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115–37. [DOI] [PubMed]

Kimball JS, Johnson JP, Carlson DA. Oxidative stress and osteoporosis. J Bone Joint Surg Am. 2021;103:1451–61. [DOI] [PubMed]

Rosen CJ. The epidemiology and pathogenesis of osteoporosis. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya Ket al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. [PubMed]

Calabrese EJ, Iavicoli I, Calabrese V. Hormesis: why it is important to biogerontologists. Biogerontology. 2012;13:215–35. [DOI] [PubMed]

Miquel S, Champ C, Day J, Aarts E, Bahr BA, Bakker M, et al. Poor cognitive ageing: vulnerabilities, mechanisms and the impact of nutritional interventions. Ageing Res Rev. 2018;42:40–55. [DOI] [PubMed]

Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal. 2010;13:1763–811. [DOI] [PubMed] [PMC]

10.

Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci. 2007;8:766–75. [DOI] [PubMed]

11.

Abdollahi M, Larijani B, Rahimi R, Salari P. Role of oxidative stress in osteoporosis. Therapy. 2005;2:787–96. [DOI]

12.

Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med. 2001;31:509–19. [DOI] [PubMed]

13.

Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, et al. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-κB. Biochem Biophys Res Commun. 2004;314:197–207. [DOI] [PubMed]

14.

Brayboy JR, Chen XW, Lee YS, Anderson JJB. The protective effects of ginkgo biloba extract (EGb 761) against free radical damage to osteoblast-like bone cells (MC3T3-E1) and the proliferative effects of EGb 761 on these cells. Nutr Res. 2001;21:1275–85. [DOI]

15.

Liu AL, Zhang ZM, Zhu BF, Liao ZH, Liu Z. Metallothionein protects bone marrow stromal cells against hydrogen peroxide-induced inhibition of osteoblastic differentiation. Cell biology international. 2004;28:905–11. [DOI] [PubMed]

16.

Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31:266–300. [DOI] [PubMed] [PMC]

17.

Steinbeck MJ, Appel WH Jr, Verhoeven AJ, Karnovsky MJ. NADPH-oxidase expression and in situ production of superoxide by osteoclasts actively resorbing bone. J Cell Biol. 1994;126:765–72. [DOI] [PubMed] [PMC]

18.

Fraser JH, Helfrich MH, Wallace HM, Ralston SH. Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae. Bone. 1996;19:223–6. [DOI] [PubMed]

19.

Suzuki H, Hayakawa M, Kobayashi K, Takiguchi H, Abiko Y. H₂O₂-derived free radicals treated fibronectin substratum reduces the bone nodule formation of rat calvarial osteoblast. Mech Ageing Dev. 1997;98:113–25. [DOI] [PubMed]

20.

Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab. 2017;14:209–16. [DOI] [PubMed] [PMC]

21.

Mann V, Huber C, Kogianni G, Collins F, Noble B. The antioxidant effect of estrogen and selective estrogen receptor modulators in the inhibition of osteocyte apoptosis in vitro. Bone. 2007;40:674–84. [DOI] [PubMed]

22.

Tretter V, Hochreiter B, Zach ML, Krenn K, Klein KU. Understanding cellular redox homeostasis: a challenge for precision medicine. Int J Mol Sci. 2021;23:106. [DOI] [PubMed] [PMC]

23.

Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48:749–62. [DOI] [PubMed] [PMC]

24.

de Mochel NS, Seronello S, Wang SH, Ito C, Zheng JX, Liang TJ, et al. Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection. Hepatology. 2010;52:47–59. [DOI] [PubMed] [PMC]

25.

Catarzi S, Romagnoli C, Marcucci G, Favilli F, Iantomasi T, Vincenzini MT. Redox regulation of ERK1/2 activation induced by sphingosine 1-phosphate in fibroblasts: involvement of NADPH oxidase and platelet-derived growth factor receptor. Biochim Biophys Acta. 2011;1810:446–56. [DOI] [PubMed]

26.

Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24:981–90. [DOI] [PubMed] [PMC]

27.

Dai Y, Ding Y, Li L. Nanozymes for regulation of reactive oxygen species and disease therapy. Chin Chem Lett. 2021;32:2715–28. [DOI]

28.

He H, Meng S, Li H, Yang Q, Xu Z, Chen X, et al. Nanoplatform based on GSH-responsive mesoporous silica nanoparticles for cancer therapy and mitochondrial targeted imaging. Mikrochim Acta. 2021;188:154. [DOI] [PubMed]

29.

Nguyen J, Tirla A, Rivera-Fuentes P. Disruption of mitochondrial redox homeostasis by enzymatic activation of a trialkylphosphine probe. Org Biomol Chem. 2021;19:2681–7. [DOI] [PubMed]

30.

Lennicke C, Cochemé HM. Redox regulation of the insulin signalling pathway. Redox Biol. 2021;42:101964. [DOI] [PubMed] [PMC]

31.

Koh JM, Lee YS, Byun CH, Chang EJ, Kim H, Kim YH, et al. Alpha-lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in human bone marrow stromal cells. J Endocrinol. 2005;185:401–13. [DOI] [PubMed]

32.

Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem. 2007;113:234–58. [DOI] [PubMed]

33.

Fontani F, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Glutathione, N-acetylcysteine and lipoic acid down-regulate starvation-induced apoptosis, RANKL/OPG ratio and sclerostin in osteocytes: involvement of JNK and ERK1/2 signalling. Calcif Tissue Int. 2015;96:335–46. [DOI] [PubMed]

34.

Sendur OF, Turan Y, Tastaban E, Serter M. Antioxidant status in patients with osteoporosis: a controlled study. Joint Bone Spine. 2009;76:514–8. [DOI] [PubMed]

35.

Lean JM, Jagger CJ, Kirstein B, Fuller K, Chambers TJ. Hydrogen peroxide is essential for estrogen-deficiency bone loss and osteoclast formation. Endocrinology. 2005;146:728–35. [DOI] [PubMed]

36.

Bellanti F, Matteo M, Rollo T, De Rosario F, Greco P, Vendemiale G, et al. Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy. Redox Biol. 2013;1:340–6. [DOI] [PubMed] [PMC]

37.

Sumi D, Hayashi T, Matsui-Hirai H, Jacobs AT, Ignarro LJ, Iguchi A. 17beta-estradiol inhibits NADPH oxidase activity through the regulation of p47phox mRNA and protein expression in THP-1 cells. Biochim Biophys Acta. 2003;1640:113–8. [DOI] [PubMed]

38.

Sheweita SA, Khoshhal KI. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab. 2007;8:519–25. [DOI] [PubMed]

39.

Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138:16–27. [DOI] [PubMed]

40.

Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y. Oxidative stress in bone remodelling and disease. Trends Mol Med. 2009;15:468–77. [DOI] [PubMed]

41.

Bjelaković G, Beninati S, Pavlović D, Kocić G, Jevtović T, Kamenov B, et al. Glucocorticoids and oxidative stress. J Basic Clin Physiol Pharmacol. 2007;18:115–27. [DOI] [PubMed]

42.

Filaire E, Toumi H. Reactive oxygen species and exercise on bone metabolism: friend or enemy? Joint Bone Spine. 2012;79:341–6. [DOI] [PubMed]

43.

Sheng MH, Lau KH, Baylink DJ. Role of osteocyte-derived insulin-like growth factor I in developmental growth, modeling, remodeling, and regeneration of the bone. J Bone Metab. 2014;21:41–54. [DOI] [PubMed] [PMC]

44.

Allen MR, Metzger CE, Ahn J, Hankenson KD. Basic bone biology. In: Guastaldi FP, Mahadik B, editors. Bone tissue engineering. Cham: Springer; 2022. pp. 13–35. [DOI]

45.

Baron R, Hesse E. Update on bone anabolics in osteoporosis treatment: rationale, current status, and perspectives. J Clin Endocrinol Metab. 2012;97:311–25. [DOI] [PubMed] [PMC]

46.

Callaway DA, Jiang JX. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases. J Bone Miner Metab. 2015;33:359–70. [DOI] [PubMed]

47.

Hyeon S, Lee H, Yang Y, Jeong W. Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation. Free Radic Biol Med. 2013;65:789–99. [DOI] [PubMed]

48.

Rana T, Schultz MA, Freeman ML, Biswas S. Loss of Nrf2 accelerates ionizing radiation-induced bone loss by upregulating RANKL. Free Radic Biol Med. 2012;53:2298–307. [DOI] [PubMed] [PMC]

49.

Baek KH, Oh KW, Lee WY, Lee SS, Kim MK, Kwon HS, et al. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int. 2010;87:226–35. [DOI] [PubMed]

50.

Ostman B, Michaëlsson K, Helmersson J, Byberg L, Gedeborg R, Melhus H, et al. Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol. Free Radic Biol Med. 2009;47:668–73. [DOI] [PubMed]

51.

Tan S, Su Y, Huang L, Deng S, Yan G, Yang X, et al. Corilagin attenuates osteoclastic osteolysis by enhancing HO-1 and inhibiting ROS. J Biochem Mol Toxicol. 2022;36:e23049. [DOI] [PubMed]

52.

Koh JM, Lee YS, Kim YS, Kim DJ, Kim HH, Park JY, et al. Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation. J Bone Miner Res. 2006;21:1003–11. [DOI] [PubMed]

53.

Hu Y, Chan E, Wang SX, Li B. Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation. Endocrinology. 2003;144:2068–74. [DOI] [PubMed]

54.

Na J, Zheng L, Wang L, Shi Q, Yang Z, Liu N, et al. Phenytoin regulates migration and osteogenic differentiation by MAPK pathway in human periodontal ligament cells. Cell Mol Bioeng. 2021;15:151–60. [DOI] [PubMed] [PMC]

55.

Cerqueni G, Scalzone A, Licini C, Gentile P, Mattioli-Belmonte M. Insights into oxidative stress in bone tissue and novel challenges for biomaterials. Mater Sci Eng C Mater Biol Appl. 2021;130:112433. [DOI] [PubMed]

56.

Wang X, Tian Y, Liang X, Yin C, Huai Y, Zhao Y, et al. Bergamottin promotes osteoblast differentiation and bone formation via activating the Wnt/β-catenin signaling pathway. Food Funct. 2022;13:2913–24. [DOI] [PubMed]

57.

Braveboy-Wagner J, Sharoni Y, Lelkes PI. Nutraceuticals synergistically promote osteogenesis in cultured 7F2 osteoblasts and mitigate inhibition of differentiation and maturation in simulated microgravity. Int J Mol Sci. 2021;23:136. [DOI] [PubMed] [PMC]

58.

Romagnoli C, Marcucci G, Favilli F, Zonefrati R, Mavilia C, Galli G, et al. Role of GSH/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast-like SaOS-2 cells. FEBS J. 2013;280:867–79. [DOI] [PubMed]

59.

Banfi G, Iorio EL, Corsi MM. Oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med. 2008;46:1550–5. [DOI] [PubMed]

60.

Jun JH, Lee SH, Kwak HB, Lee ZH, Seo SB, Woo KM, et al. N-acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells. J Cell Biochem. 2008;103:1246–55. [DOI] [PubMed]

61.

Henriksen K, Neutzsky-Wulff AV, Bonewald LF, Karsdal MA. Local communication on and within bone controls bone remodeling. Bone. 2009;44:1026–33. [DOI] [PubMed]

62.

Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26:229–38. [DOI] [PubMed] [PMC]

63.

Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2014;94:25–34. [DOI] [PubMed] [PMC]

64.

Jilka RL, Noble B, Weinstein RS. Osteocyte apoptosis. Bone. 2013;54:264–71. [DOI] [PubMed] [PMC]

65.

Mulcahy LE, Taylor D, Lee TC, Duffy GP. RANKL and OPG activity is regulated by injury size in networks of osteocyte-like cells. Bone. 2011;48:182–8. [DOI] [PubMed]

66.

Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, et al. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest. 2003;112:915–23. [DOI] [PubMed] [PMC]

67.

Udagawa N, Koide M, Nakamura M, Nakamichi Y, Yamashita T, Uehara S, et al. Osteoclast differentiation by RANKL and OPG signaling pathways. J Bone Miner Metab. 2021;39:19–26. [DOI] [PubMed]

68.

Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone. 2008;42:606–15. [DOI] [PubMed] [PMC]

69.

Rochefort GY, Pallu S, Benhamou CL. Osteocyte: the unrecognized side of bone tissue. Osteoporos Int. 2010;21:1457–69. [DOI] [PubMed]

70.

Noble B. Microdamage and apoptosis. Eur J Morphol. 2005;42:91–8. [DOI] [PubMed]

71.

Mohamad NV, Ima-Nirwana S, Chin KY. Self-emulsified annatto tocotrienol improves bone histomorphometric parameters in a rat model of oestrogen deficiency through suppression of skeletal sclerostin level and RANKL/OPG ratio. Int J Med Sci. 2021;18:3665–73. [DOI] [PubMed] [PMC]

72.

Delgado-Calle J, Bellido T. The osteocyte as a signaling cell. Physiol Rev. 2022;102:379–410. [DOI] [PubMed] [PMC]

73.

Al-Dujaili SA, Lau E, Al-Dujaili H, Tsang K, Guenther A, You L. Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro. J Cell Biochem. 2011;112:2412–23. [DOI] [PubMed]

74.

Tami AE, Nasser P, Verborgt O, Schaffler MB, Knothe Tate ML. The role of interstitial fluid flow in the remodeling response to fatigue loading. J Bone Miner Res. 2002;17:2030–7. [DOI] [PubMed]

75.

Kikuyama A, Fukuda K, Mori S, Okada M, Yamaguchi H, Hamanishi C. Hydrogen peroxide induces apoptosis of osteocytes: involvement of calcium ion and caspase activity. Calcif Tissue Int. 2002;71:243–8. [DOI] [PubMed]

76.

Hall SL, Greendale GA. The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int. 1998;63:183–9. [DOI] [PubMed]

77.

Sanders KM, Kotowicz MA, Nicholson GC. Potential role of the antioxidant N-acetylcysteine in slowing bone resorption in early post-menopausal women: a pilot study. Transl Res. 2007;150:215. [DOI] [PubMed]

78.

Karachalios T, Paridis D, Tekos F, Skaperda Z, Veskoukis AS, Kouretas D. Patients undergoing surgery for hip fractures suffer from severe oxidative stress as compared to patients with hip osteoarthritis undergoing total hip arthroplasty. Oxid Med Cell Longev. 2021;2021:5542634. [DOI] [PubMed] [PMC]

79.

El-Shal LM, El-Star AAA, Azmy AM, Elnegris HM. The possible protective role of N-acetyl cysteine on duodenal mucosa of high fat diet and orlistat treated adult male albino rats and the active role of tumor necrosis factor α (TNFα) and interleukin 6 (IL6) (histological and biochemical study). Ultrastruct Pathol. 2022;46:18–36. [DOI] [PubMed]

80.

Polat B, Halici Z, Cadirci E, Albayrak A, Karakus E, Bayir Y, et al. The effect of alpha-lipoic acid in ovariectomy and inflammation-mediated osteoporosis on the skeletal status of rat bone. Eur J Pharmacol. 2013;718:469–74. [DOI] [PubMed]

81.

Shuid AN, Mohamad S, Muhammad N, Fadzilah FM, Mokhtar SA, Mohamed N, et al. Effects of α-tocopherol on the early phase of osteoporotic fracture healing. J Orthop Res. 2011;29:1732–8. [DOI] [PubMed]

82.

Hua R, Zhang J, Riquelme MA, Jiang JX. Connexin gap junctions and hemichannels link oxidative stress to skeletal physiology and pathology. Curr Osteoporos Rep. 2021;19:66–74. [DOI] [PubMed] [PMC]

83.

Ueno T, Yamada M, Igarashi Y, Ogawa T. N-acetyl cysteine protects osteoblastic function from oxidative stress. J Biomed Mater Res A. 2011;99:523–31. [DOI] [PubMed]

84.

Sun JB, Wang Z, An WJ. Protection of icariin against hydrogen peroxide-induced MC3T3-E1 cell oxidative damage. Orthop Surg. 2021;13:632–40. [DOI] [PubMed] [PMC]

85.

Song J, Cui N, Mao X, Huang Q, Lee ES, Jiang H. Sorption studies of tetracycline antibiotics on hydroxyapatite (01) surface—a first-principles insight. Materials (Basel). 2022;15:797. [DOI] [PubMed] [PMC]

86.

Mora Raimundo P, Manzano García M, Vallet Regí M. Nanoparticles for the treatment of osteoporosis. AIMS Bioeng. 2017;4:259–74. [DOI]

87.

Wang L, Hu X, Ma X, Ma Z, Zhang Y, Lu Y, et al. Promotion of osteointegration under diabetic conditions by tantalum coating-based surface modification on 3-dimensional printed porous titanium implants. Colloids Surf B Biointerfaces. 2016;148:440–52. [DOI] [PubMed]

88.

Lyons JG, Plantz MA, Hsu WK, Hsu EL, Minardi S. Nanostructured biomaterials for bone regeneration. Front Bioeng Biotechnol. 2020;8:922. [DOI] [PubMed] [PMC]

89.

Fini M, Giavaresi G, Torricelli P, Borsari V, Giardino R, Nicolini A, et al. Osteoporosis and biomaterial osteointegration. Biomed Pharmacother. 2004;58:487–93. [DOI] [PubMed]

90.

Ogay V, Mun EA, Kudaibergen G, Baidarbekov M, Kassymbek K, Zharkinbekov Z, et al. Progress and prospects of polymer-based drug delivery systems for bone tissue regeneration. Polymers (Basel). 2020;12:2881. [DOI] [PubMed] [PMC]

91.

Cao L, Wang J, Hou J, Xing W, Liu C. Vascularization and bone regeneration in a critical sized defect using 2-N,6-O-sulfated chitosan nanoparticles incorporating BMP-2. Biomaterials. 2014;35:684–98. [DOI] [PubMed]

92.

Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16:71. [DOI] [PubMed] [PMC]

93.

Lee D, Heo DN, Kim HJ, Ko WK, Lee SJ, Heo M, et al. Inhibition of osteoclast differentiation and bone resorption by bisphosphonate-conjugated gold nanoparticles. Sci Rep. 2016;6:27336. [DOI] [PubMed] [PMC]

94.

Sun X, Wei J, Lyu J, Bian T, Liu Z, Huang J, et al. Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis. J Nanobiotechnology. 2019;17:10. [DOI] [PubMed] [PMC]

95.

Jiang T, Yu X, Carbone EJ, Nelson C, Kan HM, Lo KW. Poly aspartic acid peptide-linked PLGA based nanoscale particles: potential for bone-targeting drug delivery applications. Int J Pharm. 2014;475:547–57. [DOI] [PubMed]

96.

Liang C, Guo B, Wu H, Shao N, Li D, Liu J, et al. Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nat Med. 2015;21:288–94. [DOI] [PubMed] [PMC]

97.

Fu YC, Fu TF, Wang HJ, Lin CW, Lee GH, Wu SC, et al. Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation. Acta Biomater. 2014;10:4583–96. [DOI] [PubMed]

98.

Wang H, Liu J, Tao S, Chai G, Wang J, Hu FQ, et al. Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system. Int J Nanomedicine. 2015;10:5671–85. [DOI] [PubMed] [PMC]

99.

Cai Y, Gao T, Fu S, Sun P. Development of zoledronic acid functionalized hydroxyapatite loaded polymeric nanoparticles for the treatment of osteoporosis. Exp Ther Med. 2018;16:704–10. [DOI] [PubMed] [PMC]

100.

Beltrán-Gracia E, López-Camacho A, Higuera-Ciapara I, Velázquez-Fernández JB, Vallejo-Cardona AA. Nanomedicine review: clinical developments in liposomal applications. Cancer Nano. 2019;10:11. [DOI]

101.

Xiao L, Lin J, Chen R, Huang Y, Liu Y, Bai J, et al. Sustained release of melatonin from GelMA liposomes reduced osteoblast apoptosis and improved implant osseointegration in osteoporosis. Oxid Med Cell Longev. 2020;2020:6797154. [DOI] [PubMed] [PMC]

102.

Vhora I, Lalani R, Bhatt P, Patil S, Misra A. Lipid-nucleic acid nanoparticles of novel ionizable lipids for systemic BMP-9 gene delivery to bone-marrow mesenchymal stem cells for osteoinduction. Int J Pharm. 2019;563:324–36. [DOI] [PubMed]

103.

Shin HJ, Park H, Shin N, Kwon HH, Yin Y, Hwang JA, et al. p47phox siRNA-loaded PLGA nanoparticles suppress ROS/oxidative stress-induced chondrocyte damage in osteoarthritis. Polymers (Basel). 2020;12:443. [DOI] [PubMed] [PMC]

104.

Li L, Yu M, Li Y, Li Q, Yang H, Zheng M, et al. Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration. Bioact Mater. 2020;6:1255–66. [DOI] [PubMed] [PMC]

105.

Chen R, Liu G, Sun X, Cao X, He W, Lin X, et al. Chitosan derived nitrogen-doped carbon dots suppress osteoclastic osteolysis via downregulating ROS. Nanoscale. 2020;12:16229–44. [DOI] [PubMed]

106.

Shi D, Karmakar B, Hussein Osman HE, El-kott AF, Morsy K, Abdel-Daim MM. Design and synthesis of chitosan/agar/Ag NPs: a potent and green bio-nanocomposite for the treatment of glucocorticoid induced osteoporosis in rats. Arab J Chem. 2022;15:103471. [DOI]

107.

Santhosh S, Mukherjee D, Anbu J, Murahari M, Teja BV. Improved treatment efficacy of risedronate functionalized chitosan nanoparticles in osteoporosis: formulation development, in vivo, and molecular modelling studies. J Microencapsul. 2019;36:338–55. [DOI] [PubMed]

108.

Marycz K, Smieszek A, Marcinkowska K, Sikora M, Turlej E, Sobierajska P, et al. Nanohydroxyapatite (nHAp) doped with iron oxide nanoparticles (IO), miR-21 and miR-124 under magnetic field conditions modulates osteoblast viability, reduces inflammation and inhibits the growth of osteoclast—a novel concept for osteoporosis treatment: part 1. Int J Nanomedicine. 2021;16:3429–56. [DOI] [PubMed] [PMC]

109.

Fouad-Elhady EA, Aglan HA, Hassan RE, Ahmed HH, Sabry GM. Modulation of bone turnover aberration: a target for management of primary osteoporosis in experimental rat model. Heliyon. 2020;6:e03341. [DOI] [PubMed] [PMC]

110.

Zhu Y, Li Z, Zhang Y, Lan F, He J, Wu Y. The essential role of osteoclast-derived exosomes in magnetic nanoparticle-infiltrated hydroxyapatite scaffold modulated osteoblast proliferation in an osteoporosis model. Nanoscale. 2020;12:8720–6. [DOI] [PubMed]

111.

Sistanipour E, Meshkini A, Oveisi H. Catechin-conjugated mesoporous hydroxyapatite nanoparticle: a novel nano-antioxidant with enhanced osteogenic property. Colloids Surf B Biointerfaces. 2018;169:329–39. [DOI] [PubMed]

112.

Pinna A, Torki Baghbaderani M, Vigil Hernández V, Naruphontjirakul P, Li S, McFarlane T, et al. Nanoceria provides antioxidant and osteogenic properties to mesoporous silica nanoparticles for osteoporosis treatment. Acta Biomater. 2021;122:365–76. [DOI] [PubMed]

113.

Mora-Raimundo P, Lozano D, Benito M, Mulero F, Manzano M, Vallet-Regí M. Osteoporosis remission and new bone formation with mesoporous silica nanoparticles. Adv Sci (Weinh). 2021;8:e2101107. [DOI] [PubMed] [PMC]

114.

Gong J, Fu S, Zhou Z. Silica/OCP affects the viability of osteoblasts through ROS-induced autophagy. J Nanomater. 2021;2021:3159848. [DOI]

115.

Beck GR Jr, Ha SW, Camalier CE, Yamaguchi M, Li Y, Lee JK, et al. Bioactive silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and enhance bone mineral density in vivo. Nanomedicine. 2012;8:793–803. [DOI] [PubMed] [PMC]

116.

Lee SC, Lee NH, Patel KD, Jang TS, Knowles JC, Kim HW, et al. The effect of selenium nanoparticles on the osteogenic differentiation of MC3T3-E1 cells. Nanomaterials (Basel). 2021;11:557. [DOI] [PubMed] [PMC]

117.

Kim WK, Kim JC, Park HJ, Sul OJ, Lee MH, Kim JS, et al. Platinum nanoparticles reduce ovariectomy-induced bone loss by decreasing osteoclastogenesis. Exp Mol Med. 2012;44:432–9. [DOI] [PubMed] [PMC]

118.

Sul OJ, Kim JC, Kyung TW, Kim HJ, Kim YY, Kim SH, et al. Gold nanoparticles inhibited the receptor activator of nuclear factor-κb ligand (RANKL)-induced osteoclast formation by acting as an antioxidant. Biosci Biotechnol Biochem. 2010;74:2209–13. [DOI] [PubMed]

119.

Zhu S, Zhu L, Yu J, Wang Y, Peng B. Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo. Int J Nanomedicine. 2019;14:5017–32. [DOI] [PubMed] [PMC]

120.

Dou C, Li J, He J, Luo F, Yu T, Dai Q, et al. Bone-targeted pH-responsive cerium nanoparticles for anabolic therapy in osteoporosis. Bioact Mater. 2021;6:4697–706. [DOI] [PubMed] [PMC]