{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:49:59Z","timestamp":1792453799039,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T00:00:00Z","timestamp":1721520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["108-2320-B-037-030-MY3"],"award-info":[{"award-number":["108-2320-B-037-030-MY3"]}]},{"name":"National Science and Technology Council","award":["110-2811-B-037-515"],"award-info":[{"award-number":["110-2811-B-037-515"]}]},{"name":"National Science and Technology Council","award":["112-2320-B-037-013-"],"award-info":[{"award-number":["112-2320-B-037-013-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague\u2013Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.<\/jats:p>","DOI":"10.3390\/nu16142364","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T12:20:38Z","timestamp":1721650838000},"page":"2364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation"],"prefix":"10.3390","volume":"16","author":[{"given":"Yu-Chen","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-5862","authenticated-orcid":false,"given":"Tzu-Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Ling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung 802511, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bau-Shan","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-6355","authenticated-orcid":false,"given":"Kee-Lung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100587","DOI":"10.1016\/j.eclinm.2020.100587","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies","volume":"29\u201330","author":"Cui","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.berh.2018.10.007","article-title":"Update on the epidemiology, risk factors and disease outcomes of osteoarthritis","volume":"32","author":"McCabe","year":"2018","journal-title":"Best. Pract. Res. Clin. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116068","DOI":"10.1016\/j.bone.2021.116068","article-title":"Osteoporosis, fracture, osteoarthritis & sarcopenia: A systematic review of circulating microRNA association","volume":"152","author":"Jones","year":"2021","journal-title":"Bone"},{"key":"ref_4","first-page":"171","article-title":"Menopause and Osteoarthritis: Any Association ?","volume":"9","author":"Mahajan","year":"2018","journal-title":"J. Midlife Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s13075-023-03213-5","article-title":"Osteoporosis and osteoarthritis: A bi-directional Mendelian randomization study","volume":"25","author":"Qu","year":"2023","journal-title":"Arthritis Res. Ther."},{"key":"ref_6","first-page":"208","article-title":"Clinical manifestations of osteoarthritis in osteoporotic and osteopenic postmenopausal women","volume":"18","author":"Rizou","year":"2018","journal-title":"J. Musculoskelet. Neuronal. Interact."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s11926-024-01139-8","article-title":"Effect of Osteoporosis Treatments on Osteoarthritis Progression in Postmenopausal Women: A Review of the Literature","volume":"26","author":"Ho","year":"2024","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1001\/archinte.163.4.427","article-title":"The metabolic syndrome: Prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988\u20131994","volume":"163","author":"Park","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.joca.2012.06.006","article-title":"Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: A 3-year follow-up of the ROAD study","volume":"20","author":"Yoshimura","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3810\/pgm.2009.11.2073","article-title":"Increased prevalence of metabolic syndrome in individuals with osteoarthritis: An analysis of NHANES III data","volume":"121","author":"Puenpatom","year":"2009","journal-title":"Postgrad. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, Y., Ma, L., Yang, X., Bie, J., Li, D., Sun, C., Zhang, J., Meng, Y., and Lin, J. (2019). Menopausal Hormone Replacement Therapy and the Risk of Ovarian Cancer: A Meta-Analysis. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00801"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"m3873","DOI":"10.1136\/bmj.m3873","article-title":"Use of hormone replacement therapy and risk of breast cancer: Nested case-control studies using the QResearch and CPRD databases","volume":"371","author":"Vinogradova","year":"2020","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chen, L.R., and Chen, K.H. (2021). Utilization of Isoflavones in Soybeans for Women with Menopausal Syndrome: An Overview. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063212"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pabich, M., and Materska, M. (2019). Biological Effect of Soy Isoflavones in the Prevention of Civilization Diseases. Nutrients, 11.","DOI":"10.3390\/nu11071660"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/ajcn\/77.2.411","article-title":"Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women","volume":"77","author":"Setchell","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1753-4887.2011.00400.x","article-title":"Emerging evidence of the health benefits of S-equol, an estrogen receptor beta agonist","volume":"69","author":"Jackson","year":"2011","journal-title":"Nutr. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3892\/mmr.2013.1752","article-title":"The antioxidant activity of daidzein metabolites, Odesmethylangolensin and equol, in HepG2 cells","volume":"9","author":"Choi","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s11626-011-9464-x","article-title":"Antioxidant effect of a phytoestrogen equol on cultured muscle cells of embryonic broilers","volume":"47","author":"Wei","year":"2011","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3390\/metabo5010056","article-title":"The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol","volume":"5","author":"Rafii","year":"2015","journal-title":"Metabolites"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7632","DOI":"10.1021\/jf034427b","article-title":"Phytoestrogens modulate binding response of estrogen receptors alpha and beta to the estrogen response element","volume":"51","author":"Kostelac","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1271\/bbb.80329","article-title":"Isolation and characterization of a novel equol-producing bacterium from human feces","volume":"72","author":"Yokoyama","year":"2008","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/153537020523000302","article-title":"Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health","volume":"230","author":"Atkinson","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1207\/S15327914NC3601_5","article-title":"Interindividual variation in metabolism of soy isoflavones and lignans: Influence of habitual diet on equol production by the gut microflora","volume":"36","author":"Rowland","year":"2000","journal-title":"Nutr. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2188\/jea.10.127","article-title":"Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake","volume":"10","author":"Arai","year":"2000","journal-title":"J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/jjco\/hyh015","article-title":"Comparisons of percent equol producers between prostate cancer patients and controls: Case-controlled studies of isoflavones in Japanese, Korean and American residents","volume":"34","author":"Akaza","year":"2004","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/jn\/136.5.1347","article-title":"Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls","volume":"136","author":"Song","year":"2006","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1093\/jn\/134.10.2623","article-title":"Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice","volume":"134","author":"Fujioka","year":"2004","journal-title":"J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3164\/jcbn.12-123","article-title":"Possible role of S-equol on bone loss via amelioration of inflammatory indices in ovariectomized mice","volume":"53","author":"Nishide","year":"2013","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1097\/gme.0b013e3181f85aa7","article-title":"Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: A pilot randomized, placebo-controlled trial","volume":"18","author":"Tousen","year":"2011","journal-title":"Menopause"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Huang, L.W., Huang, T.C., Hu, Y.C., Hsieh, B.S., Cheng, H.L., Chiu, P.R., and Chang, K.L. (2021). S-Equol Protects Chondrocytes against Sodium Nitroprusside-Caused Matrix Loss and Apoptosis through Activating PI3K\/Akt Pathway. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137054"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jnutbio.2016.02.012","article-title":"Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice","volume":"32","author":"Lin","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hirase, Y., and Okubo, A. (J. Orthop. Sci., 2024). Equol production capability and family history as risk factors for hand osteoarthritis in menopausal and postmenopausal women. Cross-sectional study, J. Orthop. Sci., in press.","DOI":"10.1016\/j.jos.2024.02.001"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.joca.2008.01.002","article-title":"Animal models for osteoarthritis: The effect of ovariectomy and estrogen treatment\u2014A systematic approach","volume":"16","author":"Sniekers","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R169","DOI":"10.1186\/ar1152","article-title":"Ovariectomized rats as a model of postmenopausal osteoarthritis: Validation and application","volume":"6","author":"Tanko","year":"2004","journal-title":"Arthritis Res. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1097\/01.WCB.0000121484.18437.98","article-title":"Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM)","volume":"11","author":"Christgau","year":"2004","journal-title":"Menopause"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1002\/art.22009","article-title":"Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: Implications of the time of initiation","volume":"54","author":"Oestergaard","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1080\/01926230390241800","article-title":"Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: An animal model of osteoarthritis","volume":"31","author":"Guzman","year":"2003","journal-title":"Toxicol. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1590\/s0102-865020160110000010","article-title":"Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee","volume":"31","author":"Morais","year":"2016","journal-title":"Acta Cir. Bras."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s13075-016-1045-7","article-title":"Are estrogen-related drugs new alternatives for the management of osteoarthritis?","volume":"18","author":"Xiao","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1093\/rheumatology\/ken390","article-title":"Limited evidence for a protective effect of unopposed oestrogen therapy for osteoarthritis of the hip: A systematic review","volume":"48","author":"Schiphof","year":"2009","journal-title":"Rheumatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.maturitas.2015.09.007","article-title":"Hand osteoarthritis, menopause and menopausal hormone therapy","volume":"83","author":"Watt","year":"2016","journal-title":"Maturitas"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.maturitas.2011.03.019","article-title":"Sex hormones and structural changes in osteoarthritis: A systematic review","volume":"69","author":"Tanamas","year":"2011","journal-title":"Maturitas"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.joca.2022.12.009","article-title":"Uncovering the \u201criddle of femininity\u201d in osteoarthritis: A systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment","volume":"31","author":"Gilmer","year":"2023","journal-title":"Osteoarthr. Cartil."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chiu, P.R., Hu, Y.C., Huang, T.C., Hsieh, B.S., Yeh, J.P., Cheng, H.L., Huang, L.W., and Chang, K.L. (2016). Vitamin C Protects Chondrocytes against Monosodium Iodoacetate-Induced Osteoarthritis by Multiple Pathways. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010038"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/j.joca.2010.05.030","article-title":"The OARSI histopathology initiative\u2014Recommendations for histological assessments of osteoarthritis in the rat","volume":"18","author":"Gerwin","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","article-title":"Osteoarthritis cartilage histopathology: Grading and staging","volume":"14","author":"Pritzker","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.joca.2008.01.014","article-title":"Should subchondral bone turnover be targeted when treating osteoarthritis?","volume":"16","author":"Karsdal","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.joca.2013.03.008","article-title":"Diagnostic and prognostic value of bone biomarkers in progressive knee osteoarthritis: A 6-year follow-up study in middle-aged subjects","volume":"21","author":"Kumm","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00223-018-00512-x","article-title":"Executive summary of the European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"104","author":"Kanis","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.33176\/AACB-20-0001","article-title":"The Role of PINP in Diagnosis and Management of Metabolic Bone Disease","volume":"42","author":"Gillett","year":"2021","journal-title":"Clin. Biochem. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1530\/EJE-17-0585","article-title":"Diagnosis of Endocrine Disease: Bone turnover markers: Are they clinically useful?","volume":"178","author":"Eastell","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1136\/annrheumdis-2013-203726","article-title":"Value of biomarkers in osteoarthritis: Current status and perspectives","volume":"72","author":"Lotz","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Parisi, F., Milazzo, R., Savasi, V.M., and Cetin, I. (2021). Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041732"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4895050","DOI":"10.1155\/2016\/4895050","article-title":"A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology","volume":"2016","author":"Rose","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Riegger, J., Schoppa, A., Ruths, L., Haffner-Luntzer, M., and Ignatius, A. (2023). Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: A narrative review. Cell Mol. Biol. Lett., 28.","DOI":"10.1186\/s11658-023-00489-y"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.1002\/jcp.29607","article-title":"Role of iNOS in osteoarthritis: Pathological and therapeutic aspects","volume":"235","author":"Ahmad","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.3892\/mmr.2020.11254","article-title":"Antichondrocyte apoptosis effect of genistein in treating inflammationinduced osteoarthritis","volume":"22","author":"Zou","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Liu, F.C., Wang, C.C., Lu, J.W., Lee, C.H., Chen, S.C., Ho, Y.J., and Peng, Y.J. (2019). Chondroprotective Effects of Genistein against Osteoarthritis Induced Joint Inflammation. Nutrients, 11.","DOI":"10.3390\/nu11051180"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wu, Z., and Liu, L. (2022). The protective activity of genistein against bone and cartilage diseases. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1016981"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1007\/s10067-020-04958-z","article-title":"Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats","volume":"39","author":"Gundogdu","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1007\/s13197-020-04374-w","article-title":"Soybean isoflavone can protect against osteoarthritis in ovariectomized rats","volume":"57","author":"Toda","year":"2020","journal-title":"J. Food Sci. Technol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1363S","DOI":"10.3945\/jn.109.119784","article-title":"Equol: Pharmacokinetics and biological actions","volume":"140","author":"Setchell","year":"2010","journal-title":"J. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic. Clin. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.maturitas.2008.02.008","article-title":"Metabolic syndrome after menopause and the role of hormones","volume":"60","author":"Lobo","year":"2008","journal-title":"Maturitas"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.maturitas.2014.06.008","article-title":"Circulating leptin, resistin, adiponectin, visfatin, adipsin and ghrelin levels and insulin resistance in postmenopausal women with and without the metabolic syndrome","volume":"79","author":"Chedraui","year":"2014","journal-title":"Maturitas"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e000442","DOI":"10.1136\/rmdopen-2017-000442","article-title":"Association between osteoarthritis and dyslipidaemia: A systematic literature review and meta-analysis","volume":"3","author":"Baudart","year":"2017","journal-title":"RMD Open"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1097\/GME.0000000000001761","article-title":"Association of equol with obesity in postmenopausal women","volume":"28","author":"Takahashi","year":"2021","journal-title":"Menopause"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/ar4405","article-title":"Subchondral bone in osteoarthritis: Insight into risk factors and microstructural changes","volume":"15","author":"Li","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ncprheum0216","article-title":"Technology Insight: Adult stem cells in cartilage regeneration and tissue engineering","volume":"2","author":"Chen","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s13075-015-0793-0","article-title":"Serum hyaluronic acid concentration predicts the progression of joint space narrowing in normal knees and established knee osteoarthritis\u2014A five-year prospective cohort study","volume":"17","author":"Sasaki","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.joca.2009.06.002","article-title":"Serum hyaluronic acid as a potential marker with a predictive value for further radiographic progression of hand osteoarthritis","volume":"17","author":"Filkova","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/1529-0131(199907)42:7<1443::AID-ANR18>3.0.CO;2-A","article-title":"Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage","volume":"42","author":"Aigner","year":"1999","journal-title":"Arthritis Rheum."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/rheumatology\/kel409","article-title":"A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis--association with disease progression","volume":"46","author":"Sharif","year":"2007","journal-title":"Rheumatology"},{"key":"ref_74","first-page":"e18607","article-title":"Association of Matrix Metalloproteinase (MMP) Gene Polymorphisms With Knee Osteoarthritis: A Review of the Literature","volume":"13","author":"Milaras","year":"2021","journal-title":"Cureus"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hu, Q., and Ecker, M. (2021). Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041742"},{"key":"ref_76","first-page":"1228","article-title":"Protective effects of equol on the cartilage and subchondral bone in ovariectomized rats with osteoarthritis","volume":"25","author":"Ping","year":"2022","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1136\/annrheumdis-2013-203355","article-title":"Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: Influences of age, gender and osteoarthritis affecting other joints","volume":"73","author":"Judge","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1097\/BOR.0b013e3283494005","article-title":"Aging and osteoarthritis","volume":"23","author":"Loeser","year":"2011","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.joca.2009.09.008","article-title":"Mitochondrial DNA damage is involved in apoptosis caused by pro-inflammatory cytokines in human OA chondrocytes","volume":"18","author":"Kim","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7937","DOI":"10.4049\/jimmunol.0803991","article-title":"Increase in ALK1\/ALK5 ratio as a cause for elevated MMP-13 expression in osteoarthritis in humans and mice","volume":"182","author":"Remst","year":"2009","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.bbadis.2016.01.003","article-title":"ROS\/oxidative stress signaling in osteoarthritis","volume":"1862","author":"Lepetsos","year":"2016","journal-title":"Biochim. Biophys. 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