{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:40:56Z","timestamp":1778852456623,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>OP and OA are chronic bone diseases with high incidence in the middle-aged and elderly populations. The latest research shows that the pathological environment of OP may be involved in the aggravation of the pathological process of OA, and the pathological state of OP plays an important role in the aggravation of OA pathology. EXD is a traditional Chinese medicine decoction that has been used to treat osteoporosis. Therefore, we further study whether OA will be aggravated in the OP environment and whether EXD can alleviate OA by intervening in the OP environment. The purpose of this study was to analyze the effect of OP on OA metabolites by using metabolomic methods and to explore the intervention mechanism of EXD on osteoporotic OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Thirty-two SD rats were randomly divided into normal group, OA group, OP-OA group, and EXD group. EXD was administered by gavage. Histopathological evaluation of cartilage tissue was performed using Saffron fast green and HE staining. Western blot and qRT-PCR were used to detect the expression levels of chondrogenesis genes SOX9, COL2A1, and COMP in cartilage tissue. GC-TOFMS and LC-QTRAP-MS\/MS metabolomics methods were used to analyze the changes of metabolites in serum samples of rats in each group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>The slice results showed that the cartilage damage in the OP-OA group was more serious than that in the OA group, which was significantly relieved after EXD intervention, indicating that the cartilage damage in the OP-OA group was more severe than that in the OA group and further reduced the protein and gene expressions of cartilage markers SOX9, COL2A1, and COMP. Thirty-seven substances were identified, and gentiopicroside, emodin, quercetin, and diosmetin were analyzed as possible active components of EXD. EXD treatment significantly reduced cartilage damage and reversed the expression of these markers. Metabolomics showed that EXD attenuated cartilage destruction by modulating the expression of cystine, chenodeoxycholate, and D-Turanose, involving glycolysis\/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The OP environment may promote the progression of OA through metabolic factors. The benign intervention of EXD in osteoporotic OA involves cystine, chenodeoxycholate, and D-Turanose, and their associated glycolysis\/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways. Therefore, we have a deep understanding of the metabolic-related intervention of EXD in osteoporotic OA and are eager to better understand the mechanism of multi-targeted intervention of EXD in bone metabolic lesions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.905507","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T05:16:59Z","timestamp":1658985419000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["GCTOF-MS Combined LC-QTRAP-MS\/MS Reveals Metabolic Difference Between Osteoarthritis and Osteoporotic Osteoarthritis and the Intervention Effect of Erxian Decoction"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhenyuan","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runlin","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiyang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lishi","family":"Jie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1186\/s12889-016-3712-7","article-title":"Prevalence of Osteoporosis in China: A Meta-Analysis and Systematic Review","volume":"16","author":"Chen","year":"2016","journal-title":"BMC Public Health"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00304","article-title":"The Prevalence of Symptomatic Knee Osteoarthritis in Relation to Age, Sex, Area, Region, and Body Mass Index in China: A Systematic Review and Meta-Analysis","volume":"7","author":"Li","year":"2020","journal-title":"Front Med (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"544","DOI":"10.3390\/ijerph13060544","article-title":"BMI and BMD: The Potential Interplay Between Obesity and Bone Fragility","volume":"13","author":"Palermo","year":"2016","journal-title":"Int J Environ Res Public Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-007568","article-title":"Body Mass Index and Risk of Knee Osteoarthritis: Systematic Review and Meta-Analysis of Prospective Studies","volume":"5","author":"Zheng","year":"2015","journal-title":"BMJ Open"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200003000-00016","article-title":"Osteoporosis","author":"Lane","year":"2000","journal-title":"Clin Orthop Relat Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.10.015","article-title":"Treating Osteoporotic Osteoarthritis, or the Art of Cutting a Balding Man's Hair","volume":"28","author":"Herrero-Beaumont","year":"2020","journal-title":"Osteoarthritis Cartilage"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-013-0445-x","article-title":"Triglyceride Metabolism in Bone Tissue is Associated With Osteoblast and Osteoclast Differentiation: A Gene Expression Study","volume":"31","author":"Dragojevi\u010d","year":"2013","journal-title":"J Bone Miner Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2018.06.001","article-title":"Visfatin Alters the Cytokine and Matrix-Degrading Enzyme Profile During Osteogenic and Adipogenic MSC Differentiation","volume":"26","author":"Tsiklauri","year":"2018","journal-title":"Osteoarthritis Cartilage"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5325813","DOI":"10.1155\/2021\/5325813","article-title":"The Value of Serum Adiponectin in Osteoporotic Women: Does Weight Have an Effect","volume":"2021","author":"Roomi","year":"2021","journal-title":"J Obes"},{"key":"B11","doi-asserted-by":"publisher","first-page":"628","DOI":"10.3390\/metabo11090628","article-title":"A Distinctive Human Metabolomics Alteration Associated With Osteopenic and Osteoporotic Patients","volume":"11","author":"Aleidi","year":"2021","journal-title":"Metabolites"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.08.009","article-title":"Knee Osteoarthritis Phenotypes and Their Relevance for Outcomes: A Systematic Review","volume":"25","author":"Deveza","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"key":"B13","article-title":"Preventive Effects of Kudzu Root on Bone Loss and Cartilage Degradation in Ovariectomized Rats [Corrected]","volume":"9","author":"Luo","year":"2017","journal-title":"Am J Transl Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00776-013-0362-9","article-title":"Naringin Promotes Osteoblast Differentiation and Effectively Reverses Ovariectomy-Associated Osteoporosis","volume":"18","author":"Li","year":"2013","journal-title":"J Orthop Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/term.1911","article-title":"Effects of Naringin on the Proliferation and Osteogenic Differentiation of Human Amniotic Fluid-Derived Stem Cells","volume":"11","author":"Liu","year":"2017","journal-title":"J Tissue Eng Regener Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.09.034","article-title":"Double Directional Adjusting Estrogenic Effect of Naringin From Rhizoma Drynariae (Gusuibu)","volume":"138","author":"Guo","year":"2011","journal-title":"J Ethnopharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms12117635","article-title":"A HNMR-Based Metabonomics Study of Postmenopausal Osteoporosis and Intervention Effects of Er-Xian Decoction in Ovariectomized Rats","volume":"12","author":"Xue","year":"2011","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"6641838","DOI":"10.1155\/2021\/6641838","article-title":"Analysis of Molecular Mechanism of Erxian Decoction in Treating Osteoporosis Based on Formula Optimization Model","volume":"2021","author":"Yang","year":"2021","journal-title":"Oxid Med Cell Longev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.831894","article-title":"Uncovering Hidden Mechanisms of Different Prescriptions Treatment for Osteoporosis via Novel Bioinformatics Model and Experiment Validation","volume":"10","author":"Liu","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jep.2006.04.020","article-title":"Antiosteoporotic Activity of Er-Xian Decoction, a Traditional Chinese Herbal Formula, in Ovariectomized Rats","volume":"108","author":"Nian","year":"2006","journal-title":"J Ethnopharmacol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2147\/CIA.S117597","article-title":"Effects of Chinese Herbal Formula Erxian Decoction for Treating Osteoporosis: A Systematic Review","volume":"12","author":"Li","year":"2017","journal-title":"Clin Interv Aging"},{"key":"B22","doi-asserted-by":"publisher","first-page":"55654","DOI":"10.3791\/55654","article-title":"Preparation of Herbal Medicine: Er-Xian Decoction and Er-Xian-Containing Serum for In Vivo and In Vitro Experiments","author":"Liu","year":"2017","journal-title":"J Vis Exp"},{"key":"B23","doi-asserted-by":"publisher","first-page":"96","DOI":"10.5606\/ArchRheumatol.2017.6061","article-title":"Mechanism of TRPA1 and TRPV4 Participating in Mechanical Hyperalgesia of Rat Experimental Knee Osteoarthritis","volume":"32","author":"Xing","year":"2017","journal-title":"Arch Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26187","article-title":"Anti-Osteoporosis Activity of Sanguinarine in Preosteoblast MC3T3-E1 Cells and an Ovariectomized Rat Model","volume":"233","author":"Zhang","year":"2018","journal-title":"J Cell Physiol"},{"key":"B25","doi-asserted-by":"crossref","DOI":"10.2106\/00004623-198163010-00017","article-title":"Biochemical and Metabolic Abnormalities in Articular Cartilage From Osteoarthritic Human Hips. III. Distribution and Metabolism of Amino Sugar-Containing Macromolecules","volume":"63","author":"Mankin","year":"1981","journal-title":"J Bone Joint Surg Am"},{"key":"B26","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.semcancer.2020.04.008","article-title":"Regulation and Function of SOX9 During Cartilage Development and Regeneration","volume":"67","author":"Song","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"9596","DOI":"10.3390\/ijms21249596","article-title":"Tissue Engineering of Cartilage Using a Random Positioning Machine","volume":"21","author":"Wehland","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.3390\/ijms22052242","article-title":"COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis","volume":"22","author":"Maly","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.06.031","article-title":"Gentiopicroside Prevents Interleukin-1 Beta Induced Inflammation Response in Rat Articular Chondrocyte","volume":"172","author":"Zhao","year":"2015","journal-title":"J Ethnopharmacol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16410","article-title":"Gentiopicroside Promotes the Osteogenesis of Bone Mesenchymal Stem Cells by Modulation of \u03b2-Catenin-BMP2 Signalling Pathway","volume":"25","author":"Jiang","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"119001","DOI":"10.1016\/j.lfs.2020.119001","article-title":"Emodin Protects Knee Joint Cartilage in Rats Through Anti-Matrix Degradation Pathway: An In Vitro and In Vivo Study","volume":"269","author":"Hu","year":"2021","journal-title":"Life Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.09.024","article-title":"Quercetin Alleviates Rat Osteoarthritis by Inhibiting Inflammation and Apoptosis of Chondrocytes, Modulating Synovial Macrophages Polarization to M2 Macrophages","volume":"145","author":"Hu","year":"2019","journal-title":"Free Radic Biol Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080219","article-title":"Diosmetin Induces Human Osteoblastic Differentiation Through the Protein Kinase C\/p38 and Extracellular Signal-Regulated Kinase 1\/2 Pathway","volume":"23","author":"Hsu","year":"2008","journal-title":"J Bone Miner Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6596","article-title":"Diosmetin Exhibits Anti-Proliferative and Anti-Inflammatory Effects on TNF-\u03b1-Stimulated Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Through Regulating the Akt and NF-\u03bab Signaling Pathways","volume":"34","author":"Chen","year":"2020","journal-title":"Phytother Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.freeradbiomed.2017.02.041","article-title":"Wogonin, a Plant Derived Small Molecule, Exerts Potent Anti-Inflammatory and Chondroprotective Effects Through the Activation of ROS\/ERK\/Nrf2 Signaling Pathways in Human Osteoarthritis Chondrocytes","volume":"106","author":"Khan","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2615","article-title":"Wogonin Inhibits Osteoclast Differentiation by Inhibiting NFATc1 Translocation Into the Nucleus","volume":"10","author":"Geng","year":"2015","journal-title":"Exp Ther Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.3390\/nu12072075","article-title":"Osteoprotective Activity and Metabolite Fingerprint via UPLC\/MS and GC\/MS of Lepidium Sativum in Ovariectomized Rats","volume":"12","author":"Abdallah","year":"2020","journal-title":"Nutrients"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.05.010","article-title":"GC-MS Method for Metabolic Profiling of Mouse Femoral Head Articular Cartilage Reveals Distinct Effects of Tissue Culture and Development","volume":"27","author":"Batushansky","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1177\/1535370220985468","article-title":"Metabolic Utilization of Human Osteoblast Cell Line hFOB 1.19 Under Normoxic and Hypoxic Conditions: A Phenotypic Microarray Analysis","volume":"246","author":"Cui","year":"2021","journal-title":"Exp Biol Med (Maywood)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23069","article-title":"Sulfasalazine Attenuates ACL Transection and Medial Menisectomy-Induced Cartilage Destruction by Inhibition of Cystine\/Glutamate Antiporter","volume":"34","author":"Tsai","year":"2016","journal-title":"J Orthop Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"780149","DOI":"10.1155\/2015\/780149","article-title":"Therapeutic Effect of Chenodeoxycholic Acid in an Experimental Rabbit Model of Osteoarthritis","volume":"2015","author":"Yan","year":"2015","journal-title":"Mediators Inflamm"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.905507\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T05:17:06Z","timestamp":1658985426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.905507\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":41,"alternative-id":["10.3389\/fendo.2022.905507"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.905507","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]},"article-number":"905507"}}