{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:40:22Z","timestamp":1792176022104,"version":"4.4.0"},"reference-count":121,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health to IRCCS Policlinico San Donato"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Bone is a very dynamic tissue, subject to continuous renewal to maintain homeostasis through bone remodeling, a process promoted by two cell types: osteoblasts, of mesenchymal derivation, are responsible for the deposition of new material, and osteoclasts, which are hematopoietic cells, responsible for bone resorption. Osteomyelitis (OM) is an invasive infectious process, with several etiological agents, the most common being Staphylococcus aureus, affecting bone or bone marrow, and severely impairing bone homeostasis, resulting in osteolysis. One of the characteristic features of OM is a strong state of oxidative stress (OS) with severe consequences on the delicate balance between osteoblastogenesis and osteoclastogenesis. Here we describe this, analyzing the effects of OS in bone remodeling and discussing the need for new, easy-to-measure and widely available OS biomarkers that will provide valid support in the management of the disease.<\/jats:p>","DOI":"10.3390\/antiox11061061","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:05:07Z","timestamp":1653635107000},"page":"1061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Osteomyelitis, Oxidative Stress and Related Biomarkers"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-7095","authenticated-orcid":false,"given":"Luca","family":"Massaccesi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences for Health, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0764-3178","authenticated-orcid":false,"given":"Emanuela","family":"Galliera","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"},{"name":"IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Centre for Reconstructive Surgery and Osteoarticular Infections, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Banfi","sequence":"additional","affiliation":[{"name":"IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7928-7697","authenticated-orcid":false,"given":"Massimiliano","family":"Corsi Romanelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"},{"name":"Service of Laboratory Medicine1-Clinical Pathology, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.0105-2896.2005.00336.x","article-title":"Osteoclast precursors, RANKL\/RANK, and immunology","volume":"208","author":"Xing","year":"2005","journal-title":"Immunol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.2741\/2252","article-title":"Osteoclast differentiation and gene regulation","volume":"12","author":"Zhao","year":"2007","journal-title":"Front. Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2215\/CJN.04151206","article-title":"Normal Bone Anatomy and Physiology The Skeleton","volume":"3","author":"Clarke","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1172\/JCI68062","article-title":"Steroids and osteoporosis: The quest for mechanisms","volume":"123","author":"Manolagas","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1172\/JCI93356","article-title":"Inflammatory osteolysis: A conspiracy against bone","volume":"127","author":"Mbalaviele","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41577-019-0178-8","article-title":"Osteoimmunology: Evolving concepts in bone-immune interactions in health and disease","volume":"19","author":"Tsukasaki","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/JLB.1AB0120-212RR","article-title":"Longitudinal evaluation of Wnt inhibitors and comparison with others serum osteoimmunological biomarkers in osteolytic bone metastasis","volume":"108","author":"Galliera","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jocd.2018.05.039","article-title":"A Prospective Assessment of Periprosthetic Bone Mineral Density and Osteoimmunological Biomarkers Variations after Total Knee Replacement Surgery","volume":"22","author":"Cucchi","year":"2019","journal-title":"J. Clin. Densitom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s11914-019-00548-4","article-title":"Mechanisms of Immune Evasion and Bone Tissue Colonization That Make Staphylococcus aureus the Primary Pathogen in Osteomyelitis","volume":"17","author":"Muthukrishnan","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jgar.2021.03.030","article-title":"Staphylococcus aureus clones causing osteomyelitis: A literature review (2000\u20132020)","volume":"26","author":"Monaco","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00934149","article-title":"Post-traumatic osteomyelitis. Pathophysiology and management","volume":"108","author":"Roesgen","year":"1989","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/QCO.0000000000000155","article-title":"Current concepts in pathogenesis of acute and chronic osteomyelitis","volume":"28","author":"Smeets","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00068-016-0694-1","article-title":"The role of biofilm on orthopaedic implants: The \u2018Holy Grail\u2019 of post-traumatic infection management?","volume":"42","author":"Mauffrey","year":"2016","journal-title":"Eur. J. Trauma Emerg. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0140-6736(04)16727-5","article-title":"Osteomyelitis","volume":"364","author":"Lew","year":"2004","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1148\/radiol.2017151929","article-title":"Hematogenous Osteomyelitis in Infants and Children: Imaging of a Changing Disease","volume":"283","author":"Jaramillo","year":"2017","journal-title":"Radiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1006\/mpat.1995.0075","article-title":"Internalization of Staphylococcus aureus by cultured osteoblasts","volume":"19","author":"Hudson","year":"1995","journal-title":"Microb. Pathog."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-94-007-0940-9_7","article-title":"Adhesion mechanisms of staphylococci","volume":"715","author":"Heilmann","year":"2011","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Claro, T., Widaa, A., O\u2019Seaghdha, M., Miajlovic, H., Foster, T.J., O\u2019Brien, F.J., and Kerrigan, S.W. (2011). Staphylococcus aureus protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018748"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1574-6968.2000.tb09096.x","article-title":"Intracellular Staphylococcus aureus induces apoptosis in mouse osteoblasts","volume":"186","author":"Tucker","year":"2000","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Widaa, A., Claro, T., Foster, T.J., O\u2019Brien, F.J., and Kerrigan, S.W. (2012). Staphylococcus aureus protein A plays a critical role in mediating bone destruction and bone loss in osteomyelitis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040586"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1128\/iai.50.1.218-224.1985","article-title":"Bacterial adherence to human endothelial cells in vitro","volume":"50","author":"Ogawa","year":"1985","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.micinf.2007.01.002","article-title":"Invasion of bone cells by Staphylococcus epidermidis","volume":"9","author":"Khalil","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/cmi.12233","article-title":"Cytoplasmic replication of Staphylococcus aureus upon phagosomal escape triggered by phenol-soluble modulin \u03b1","volume":"16","author":"Grosz","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.chom.2013.05.003","article-title":"A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis","volume":"13","author":"Cassat","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rasigade, J.P., Trouillet-Assant, S., Ferry, T., Diep, B.A., Sapin, A., Lhoste, Y., Ranfaing, J., Badiou, C., Benito, Y., and Bes, M. (2013). PSMs of hypervirulent Staphylococcus aureus act as intracellular toxins that kill infected osteoblasts. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063176"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nri2062","article-title":"Osteoimmunology: Shared mechanisms and crosstalk between the immune and bone systems","volume":"7","author":"Takayanagi","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1099\/mic.0.063016-0","article-title":"Staphylococcus aureus protein A binding to osteoblast tumour necrosis factor receptor 1 results in activation of nuclear factor kappa B and release of interleukin-6 in bone infection","volume":"159","author":"Claro","year":"2013","journal-title":"Microbiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000354440","article-title":"Staphylococcal protein A, Panton-Valentine leukocidin and coagulase aggravate the bone loss and bone destruction in osteomyelitis","volume":"32","author":"Jin","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sanchez, C.J., Ward, C.L., Romano, D.R., Hurtgen, B.J., Hardy, S.K., Woodbury, R.L., Trevino, A.V., Rathbone, C.R., and Wenke, J.C. (2013). Staphylococcus aureus biofilms decrease osteoblast viability, inhibits osteogenic differentiation, and increases bone resorption in vitro. BMC Musculoskelet. Disord., 14.","DOI":"10.1186\/1471-2474-14-187"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1159\/000366387","article-title":"Involvement of toll-like receptor 2 and pro-apoptotic signaling pathways in bone remodeling in osteomyelitis","volume":"34","author":"Chen","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1128\/IAI.69.3.1581-1586.2001","article-title":"Staphylococcus aureus and Salmonella enterica serovar Dublin induce tumor necrosis factor-related apoptosis-inducing ligand expression by normal mouse and human osteoblasts","volume":"69","author":"Alexander","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.bone.2010.11.015","article-title":"Causative agents of osteomyelitis induce death domain-containing TNF-related apoptosis-inducing ligand receptor expression on osteoblasts","volume":"48","author":"Young","year":"2011","journal-title":"Bone"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Alexander, E.H., Rivera, F.A., Marriott, I., Anguita, J., Bost, K.L., and Hudson, M.C. (2003). Staphylococcus aureus\u2014Induced tumor necrosis factor\u2014Related apoptosis\u2014Inducing ligand expression mediates apoptosis and caspase-8 activation in infected osteoblasts. BMC Microbiol., 3.","DOI":"10.1186\/1471-2180-3-5"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1302\/0301-620X.85B6.13509","article-title":"Intracellular Staphyloccus aureus","volume":"85","author":"Ellington","year":"2003","journal-title":"J. Bone Jt. Surg. Ser. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1128\/IAI.00228-08","article-title":"Staphylococcus aureus induces expression of receptor activator of NF-kappaB ligand and prostaglandin E2 in infected murine osteoblasts","volume":"76","author":"Somayaji","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41413-022-00201-4","article-title":"PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoar-thritis","volume":"10","author":"Jiang","year":"2022","journal-title":"Bone Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrd3669","article-title":"Inflammatory bone loss: Pathogenesis and therapeutic intervention","volume":"11","author":"Redlich","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3109\/08820139.2013.822766","article-title":"The role of cytokines in inflammatory bone loss","volume":"42","author":"Souza","year":"2013","journal-title":"Immunol. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10522-008-9211-1","article-title":"Effect of age on cytokine response in an experimental model of osteomyelitis","volume":"10","author":"Castro","year":"2009","journal-title":"Biogerontology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/S0002-9440(10)63226-9","article-title":"Osteoblasts express the inflammatory cytokine interleukin-6 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue","volume":"164","author":"Marriott","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1006\/cyto.2002.1039","article-title":"Local levels of interleukin-1beta, -4, -6 and tumor necrosis factor alpha in an experimental model of murine osteomyelitis due to staphylococcus aureus","volume":"19","author":"Yoshii","year":"2002","journal-title":"Cytokine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fcimb.2015.00085","article-title":"Staphylococcus aureus vs. Osteoblast: Relationship and Consequences in Osteomyelitis","volume":"5","author":"Josse","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1093\/infdis\/jiu386","article-title":"Dual impact of live Staphylococcus aureus on the osteoclast lineage, leading to increased bone resorption","volume":"211","author":"Gallet","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/08916930701694469","article-title":"Taking a toll on the bones: Regulation of bone metabolism by innate immune regulators","volume":"41","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1086\/515313","article-title":"Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the acute-phase response in patients with bacterial and tuberculous osteomyelitis","volume":"177","author":"Evans","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1046\/j.1365-2567.2001.01261.x","article-title":"Nitric oxide and bone","volume":"103","author":"Hof","year":"2001","journal-title":"Immunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.niox.2006.06.005","article-title":"The NOS3 (27-bp repeat, intron 4) polymorphism is associated with susceptibility to osteomyelitis","volume":"16","author":"Asensi","year":"2007","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/jbmr.5650100708","article-title":"Nitric oxide: A cytokine-induced regulator of bone resorption","volume":"10","author":"Ralston","year":"1995","journal-title":"J. Bone Miner. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0891-5849(01)00610-4","article-title":"Oxidative stress modulates osteoblastic differentiation of vascular and bone cells","volume":"31","author":"Mody","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1080\/00016470310013941","article-title":"Activated PMNs lead to oxidative stress on chondrocytes: A study of swine knees","volume":"74","author":"Borsiczky","year":"2003","journal-title":"Acta Orthop. Scand."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.molmed.2009.08.004","article-title":"Oxidative stress in bone remodelling and disease","volume":"15","author":"Wauquier","year":"2009","journal-title":"Trends Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1089\/ars.2013.5228","article-title":"The free radical theory of aging is dead. Long live the damage theory!","volume":"20","author":"Gladyshev","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Agidigbi, T.S., and Kim, C. (2019). Reactive Oxygen Species in Osteoclast Differentiation and Possible Pharmaceutical Targets of ROS-Mediated Osteoclast Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143576"},{"key":"ref_55","first-page":"BC08","article-title":"Free radicals and antioxidant status in chronic osteomyelitis patients: A case control study","volume":"9","author":"Jyoti","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_56","unstructured":"Tsourdi, E., J\u00e4hn, K., Rauner, M., Busse, B., and Bonewald, L.F. (2022, April 23). Physiological and Pathological Osteocytic Osteolysis. Available online: http:\/\/www.ismni.org."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1128\/mBio.00415-18","article-title":"Novel Insights into Staphylococcus aureus Deep Bone Infections: The Involvement of Osteocytes","volume":"9","author":"Yang","year":"2018","journal-title":"MBio"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/icb.2010.158","article-title":"CXCR3 ligands: Redundant, collaborative and antagonistic functions","volume":"89","author":"Groom","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/BOR.0000000000000456","article-title":"Targeting aging for disease modification in osteoarthritis","volume":"30","author":"Collins","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1042\/CS20160897","article-title":"Redox theory of aging: Implications for health and disease","volume":"131","author":"Go","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00296-007-0452-0","article-title":"Total oxidative\/anti-oxidative status and relation to bone mineral density in osteoporosis","volume":"28","author":"Altindag","year":"2008","journal-title":"Rheumatol. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jbmr.5650110515","article-title":"Osteoclastic superoxide production and bone resorption: Stimulation and inhibition by modulators of NADPH oxidase","volume":"11","author":"Darden","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1182\/blood-2004-09-3662","article-title":"A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation","volume":"106","author":"Lee","year":"2005","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00774-015-0656-4","article-title":"Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases","volume":"33","author":"Callaway","year":"2015","journal-title":"J. Bone Miner. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.freeradbiomed.2018.08.036","article-title":"NADPH oxidases in bone homeostasis and osteoporosis","volume":"132","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1172\/JCI114485","article-title":"Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo","volume":"85","author":"Garrett","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1161\/CIRCRESAHA.111.243972","article-title":"Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system","volume":"110","author":"Griendling","year":"2012","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"20030","DOI":"10.1074\/jbc.M116.731216","article-title":"NADPH Oxidases Are Essential for Macrophage Differentiation","volume":"291","author":"Xu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"38014","DOI":"10.1038\/srep38014","article-title":"NADPH oxidase gp91phox contributes to RANKL-induced osteoclast differentiation by upregulating NFATc1","volume":"6","author":"Kang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"904","DOI":"10.14348\/molcells.2015.0177","article-title":"NRROS Negatively Regulates Osteoclast Differentiation by Inhibiting RANKL-Mediated NF-N:B and Reactive Oxygen Species Pathways","volume":"38","author":"Kim","year":"2015","journal-title":"Mol. Cells"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/jcb.20048","article-title":"Expression of Nox4 in osteoclasts","volume":"92","author":"Yang","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.1172\/JCI67603","article-title":"NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis","volume":"123","author":"Goettsch","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1756-8722-6-19","article-title":"Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers","volume":"6","author":"Li","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.redox.2014.02.006","article-title":"Hydrogen peroxide sensing, signaling and regulation of transcription factors","volume":"2","author":"Marinho","year":"2014","journal-title":"Redox Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.redox.2015.01.002","article-title":"Oxidative stress: A concept in redox biology and medicine","volume":"4","author":"Sies","year":"2015","journal-title":"Redox Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s00223-010-9393-9","article-title":"Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures","volume":"87","author":"Baek","year":"2010","journal-title":"Calcif. Tissue Int."},{"key":"ref_78","first-page":"6681","article-title":"Upregulation of SIRT1 inhibits H2O2-induced osteoblast apoptosis via FoxO1\/\u03b2-catenin pathway","volume":"17","author":"Yao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/03008207.2017.1290085","article-title":"Osteoblast-osteoclast interactions","volume":"59","author":"Chen","year":"2018","journal-title":"Connect. Tissue Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ohyama, Y., Ito, J., Kitano, V.J., Shimada, J., and Hakeda, Y. (2018). The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191192"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1515\/CCLM.2008.302","article-title":"Oxidative stress, free radicals and bone remodeling","volume":"46","author":"Banfi","year":"2008","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/febs.12075","article-title":"Role of GSH\/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast-like SaOS-2 cells","volume":"280","author":"Romagnoli","year":"2013","journal-title":"FEBS J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bone.2012.11.038","article-title":"Osteocyte apoptosis","volume":"54","author":"Jilka","year":"2013","journal-title":"Bone"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbrc.2003.12.073","article-title":"Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB","volume":"314","author":"Bai","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00223-015-9961-0","article-title":"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","volume":"96","author":"Fontani","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00223-013-9774-y","article-title":"Osteocyte-driven bone remodeling","volume":"94","author":"Bellido","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bone.2010.09.014","article-title":"RANKL and OPG activity is regulated by injury size in networks of osteocyte-like cells","volume":"48","author":"Mulcahy","year":"2011","journal-title":"Bone"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1210\/en.2004-1021","article-title":"Hydrogen peroxide is essential for estrogen-deficiency bone loss and osteoclast formation","volume":"146","author":"Lean","year":"2005","journal-title":"Endocrinology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"438","DOI":"10.22203\/eCM.v042a27","article-title":"Vertebral osteomyelitis is characterised by increased RANK\/OPG and RANKL\/OPG expression ratios in vertebral bodies and intervertebral discs","volume":"42","author":"Lang","year":"2021","journal-title":"Eur. Cell. Mater."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S0006-291X(05)80311-0","article-title":"Stimulation of osteoclastic bone resorption by hydrogen peroxide","volume":"183","author":"Bax","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.yexcr.2004.07.035","article-title":"Reactive oxygen species mediate RANK signaling in osteoclasts","volume":"301","author":"Ha","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3389\/fncel.2016.00301","article-title":"NOX Activation by Subunit Interaction and Underlying Mechanisms in Disease","volume":"10","author":"Rastogi","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5111","DOI":"10.1021\/bi500331y","article-title":"Nox4: A hydrogen peroxide-generating oxygen sensor","volume":"53","author":"Nisimoto","year":"2014","journal-title":"Biochemistry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.5435\/JAAOS-D-15-00714","article-title":"Update in Pediatric Musculoskeletal Infections: When It Is, When It Isn\u2019t, and What to Do","volume":"24","author":"Arkader","year":"2016","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1097\/BPO.0b013e3181bd1e0c","article-title":"Community-associated methicillin-resistant Staphylococcus aureus in acute musculoskeletal infection in children: A game changer","volume":"29","author":"Have","year":"2009","journal-title":"J. Pediatr. Orthop."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/BPO.0b013e31817bb816","article-title":"Changing trends in acute osteomyelitis in children: Impact of methicillin-resistant Staphylococcus aureus infections","volume":"28","author":"Ahmad","year":"2008","journal-title":"J. Pediatr. Orthop."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/iwj.12545","article-title":"The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis","volume":"14","author":"Nichols","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e526","DOI":"10.1097\/BPO.0000000000002052","article-title":"The Use of Biomarkers in the Early Diagnosis of Septic Arthritis and Osteomyelitis\u2014A Pilot Study","volume":"42","author":"Mo","year":"2022","journal-title":"J. Pediatr. Orthop."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/annrheumdis-2011-201177","article-title":"Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: Data from CHECK, a cohort study of early osteoarthritis","volume":"72","author":"Lafeber","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1089\/107999001300177484","article-title":"Monocyte chemoattractant protein-1 expression by osteoblasts following infection with Staphylococcus aureus or Salmonella","volume":"21","author":"Bost","year":"2001","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.bone.2005.05.011","article-title":"Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue","volume":"37","author":"Marriott","year":"2005","journal-title":"Bone"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.archoralbio.2014.02.015","article-title":"Angiotensin II induces mitochondrial dysfunction and promotes apoptosis via JNK signalling pathway in primary mouse calvaria osteoblast","volume":"59","author":"Li","year":"2014","journal-title":"Arch. Oral Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cbi.2017.12.024","article-title":"Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis","volume":"281","author":"Phull","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/abbs\/gmaa098","article-title":"ROS signaling cascades: Dual regulations for osteoclast and osteoblast","volume":"52","author":"Tao","year":"2020","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.4049\/jimmunol.1900953","article-title":"Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis","volume":"204","author":"Kralova","year":"2020","journal-title":"J. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"975061","DOI":"10.1155\/2014\/975061","article-title":"Sequential analysis of oxidative stress markers and vitamin C status in acute bacterial osteomyelitis","volume":"2014","author":"Grbic","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/jcla.20473","article-title":"Serum paraoxonase and arylesterase activities in various forms of hepatitis B virus infection","volume":"25","author":"Duygu","year":"2011","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1179\/135100008X308911","article-title":"Assessment of paraoxonase activities in patients with knee osteoarthritis","volume":"13","author":"Soran","year":"2008","journal-title":"Redox Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/00365513.2012.700058","article-title":"The activity of paraoxonase and arylesterase in patients with osteomyelitis","volume":"72","author":"Koruk","year":"2012","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1161\/01.ATV.21.4.473","article-title":"Paraoxonase and atherosclerosis","volume":"21","author":"Durrington","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41413-019-0061-z","article-title":"Evolving concepts in bone infection: Redefining \u2018biofilm\u2019, \u2018acute vs. chronic osteomyelitis\u2019, \u2018the immune proteome\u2019 and \u2018local antibiotic therapy\u2019","volume":"7","author":"Masters","year":"2019","journal-title":"Bone Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/j.1365-2362.2006.01727.x","article-title":"Paraoxonase and arylesterase activities in coronary artery disease","volume":"36","author":"Gur","year":"2006","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1152\/physrev.1985.65.2.238","article-title":"Absorption, transport, and hepatic metabolism of copper and zinc: Special reference to metallothionein and ceruloplasmin","volume":"65","author":"Cousins","year":"1985","journal-title":"Physiol. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1089\/ars.2011.3999","article-title":"Superoxide dismutases: Role in redox signaling, vascular function, and diseases","volume":"15","author":"Fukai","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchromb.2017.08.033","article-title":"Detection of 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of oxidative damage in peripheral leukocyte DNA by UHPLC-MS\/MS","volume":"1064","author":"Wu","year":"2017","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/10590500902885684","article-title":"8-hydroxy-2\u2032-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis","volume":"27","author":"Valavanidis","year":"2009","journal-title":"J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev."},{"key":"ref_117","first-page":"e14704","article-title":"The levels of oxidative DNA damage and some antioxidants in chronic osteomyelitis patients: A cross-sectional study","volume":"75","author":"Demir","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Chen, Y., Sun, J., Dou, C., Li, N., Kang, F., Wang, Y., Cao, Z., Yang, X., and Dong, S. (2016). Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091516"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"18572","DOI":"10.1038\/srep18572","article-title":"Apocynin suppression of NADPH oxidase reverses the aging process in mesenchymal stem cells to promote osteogenesis and increase bone mass","volume":"5","author":"Sun","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1165\/ajrcmb.11.1.8018341","article-title":"Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol","volume":"11","author":"Stolk","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"22389","DOI":"10.1038\/srep22389","article-title":"A novel pyrazole derivative protects from ovariectomy-induced osteoporosis through the inhibition of NADPH oxidase","volume":"6","author":"Joo","year":"2016","journal-title":"Sci. Rep."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/6\/1061\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:19:31Z","timestamp":1760138371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/6\/1061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":121,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["antiox11061061"],"URL":"https:\/\/doi.org\/10.3390\/antiox11061061","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]}}}