{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:23:58Z","timestamp":1783524238904,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006227","name":"Lawrence Livermore National Laboratory","doi-asserted-by":"publisher","award":["LDRD 16-ERD-007"],"award-info":[{"award-number":["LDRD 16-ERD-007"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006227","name":"Lawrence Livermore National Laboratory","doi-asserted-by":"publisher","award":["LDRD 20-LW-002"],"award-info":[{"award-number":["LDRD 20-LW-002"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a painful and debilitating disease characterized by the chronic and progressive degradation of articular cartilage. Post-traumatic OA (PTOA) is a secondary form of OA that develops in ~50% of cases of severe articular injury. Inflammation and re-occurring injury have been implicated as contributing to the progression of PTOA after the initial injury. However, there is very little known about external factors prior to injury that could affect the risk of PTOA development. To examine how the gut microbiome affects PTOA development we used a chronic antibiotic treatment regimen starting at weaning for six weeks prior to ACL rupture, in mice. A six-weeks post-injury histological examination showed more robust cartilage staining on the antibiotic (AB)-treated mice than the untreated controls (VEH), suggesting slower disease progression in AB cohorts. Injured joints also showed an increase in the presence of anti-inflammatory M2 macrophages in the AB group. Molecularly, the phenotype correlated with a significantly lower expression of inflammatory genes Tlr5, Ccl8, Cxcl13, and Foxo6 in the injured joints of AB-treated animals. Our results indicate that a reduced state of inflammation at the time of injury and a lower expression of Wnt signaling modulatory protein, Rspo1, caused by AB treatment can slow down or improve PTOA outcomes.<\/jats:p>","DOI":"10.3390\/ijms21176424","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T11:22:43Z","timestamp":1599132163000},"page":"6424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Antibiotic Treatment Prior to Injury Improves Post-Traumatic Osteoarthritis Outcomes in Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Melanie E.","family":"Mendez","sequence":"first","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa K.","family":"Murugesh","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7822-7040","authenticated-orcid":false,"given":"Aimy","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-3193","authenticated-orcid":false,"given":"Nicholas R.","family":"Hum","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"},{"name":"UC Merced, School of Natural Sciences, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Summer A.","family":"McCloy","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaine A.","family":"Christiansen","sequence":"additional","affiliation":[{"name":"UC Davis Medical Center, Department of Orthopedic Surgery, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-5561","authenticated-orcid":false,"given":"Gabriela G.","family":"Loots","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA"},{"name":"UC Merced, School of Natural Sciences, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Part 1: The Human Gut Microbiome in Health and Disease","volume":"13","author":"Bull","year":"2014","journal-title":"Integr. Med. (Encinitas)"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14.","DOI":"10.1101\/036103"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fped.2019.00047","article-title":"Shaping the Gut Microbiota by Breastfeeding: The Gateway to Allergy Prevention?","volume":"7","author":"Garssen","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.alit.2017.07.010","article-title":"Development of the gut microbiota in infancy and its impact on health in later life","volume":"66","author":"Tanaka","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.cell.2012.01.035","article-title":"The impact of the gut microbiota on human health: An integrative view","volume":"148","author":"Clemente","year":"2012","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13099-018-0230-4","article-title":"Involvement of gut microbiome in human health and disease: Brief overview, knowledge gaps and research opportunities","volume":"10","author":"Liang","year":"2018","journal-title":"Gut Pathog."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-018-1703-4","article-title":"The role of the microbiome for human health: From basic science to clinical applications","volume":"57","author":"Mohajeri","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1615\/CritRevImmunol.v28.i4.20","article-title":"Understanding how lipopolysaccharide impacts CD4 T-cell immunity","volume":"28","author":"McAleer","year":"2008","journal-title":"Crit. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/cei.12839","article-title":"Activation of inflammatory immune gene cascades by lipopolysaccharide (LPS) in the porcine colonic tissue ex-vivo model","volume":"186","author":"Bahar","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mendez, M.E., Sebastian, A., Murugesh, D.K., Hum, N.R., McCool, J.L., Hsia, A.W., Christiansen, B.A., and Loots, G.G. (2020). LPS-induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice. J. Bone Miner. Res.","DOI":"10.1002\/jbmr.4117"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s12072-010-9219-x","article-title":"The role of lipopolysaccharide\/toll-like receptor 4 signaling in chronic liver diseases","volume":"4","author":"Soares","year":"2010","journal-title":"Hepatol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Calil, I.L., Zarpelon, A.C., Guerrero, A.T.G., Alves-Filho, J.C., Ferreira, S.H., Cunha, F.Q., Cunha, T.M., and Verri, W.A. (2014). Lipopolysaccharide induces inflammatory hyperalgesia triggering a TLR4\/MyD88-dependent cytokine cascade in the mice paw. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090013"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen recognition and inflammatory signaling in innate immune defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Maslanik, T., Tannura, K., Mahaffey, L., Loughridge, A.B., Beninson, L., Benninson, L., Ursell, L., Greenwood, B.N., Knight, R., and Fleshner, M. (2012). Commensal bacteria and MAMPs are necessary for stress-induced increases in IL-1\u03b2 and IL-18 but not IL-6, IL-10 or MCP-1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050636"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.immuni.2011.02.011","article-title":"Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2","volume":"34","author":"Chen","year":"2011","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ni.2635","article-title":"Innate immune recognition of the microbiota promotes host-microbial symbiosis","volume":"14","author":"Chu","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3389\/fimmu.2013.00141","article-title":"Host and microbial factors in regulation of T cells in the intestine","volume":"4","author":"Kim","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"181849","DOI":"10.1155\/2013\/181849","article-title":"Immunological Reaction in TNF-\u03b1-Mediated Osteoclast Formation and Bone Resorption In Vitro and In Vivo","volume":"2013","author":"Kitaura","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1002\/jcp.24340","article-title":"Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice","volume":"228","author":"McCabe","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-3-319-66653-2_5","article-title":"Immunology of Gut-Bone Signaling","volume":"1033","author":"Collins","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/odi.12592","article-title":"PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and in vivo","volume":"23","author":"Teramachi","year":"2017","journal-title":"Oral. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1172\/JCI87430","article-title":"From the gut to the strut: Where inflammation reigns, bone abstains","volume":"126","author":"Iqbal","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.clim.2015.03.019","article-title":"The intestinal microbiome and skeletal fitness: Connecting bugs and bones","volume":"159","author":"Charles","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/jbmr.3635","article-title":"Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption","volume":"34","author":"Schepper","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Schott, E.M., Farnsworth, C.W., Grier, A., Lillis, J.A., Soniwala, S., Dadourian, G.H., Bell, R.D., Doolittle, M.L., Villani, D.A., and Awad, H. (2018). Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight, 3.","DOI":"10.1172\/jci.insight.95997"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.joca.2018.07.020","article-title":"The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis","volume":"27","author":"Guss","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.joca.2018.05.016","article-title":"Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice","volume":"26","author":"Ulici","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e01134","DOI":"10.1016\/j.heliyon.2019.e01134","article-title":"A correlation between intestinal microbiota dysbiosis and osteoarthritis","volume":"5","author":"Szychlinska","year":"2019","journal-title":"Heliyon"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hahn, A.K., Wallace, C.W., Welhaven, H.D., Brooks, E., McAlpine, M., Christiansen, B.A., Walk, S.T., and June, R.K. (2020). The microbiome mediates subchondral bone loss and metabolomic changes after acute joint trauma. bioRxiv.","DOI":"10.1101\/2020.05.08.084822"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/jor.23341","article-title":"Review of current understanding of post-traumatic osteoarthritis resulting from sports injuries","volume":"35","author":"Carbone","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/bonekey.2014.119","article-title":"Osteoarthritis and bone mineral density: Are strong bones bad for joints?","volume":"4","author":"Hardcastle","year":"2015","journal-title":"Bonekey Rep."},{"key":"ref_32","unstructured":"(2017). Outpatient Antibiotic Prescriptions \u2014 United States, 2017."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.joca.2012.04.014","article-title":"Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis","volume":"20","author":"Christiansen","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/jor.22480","article-title":"Comparison of loading rate-dependent injury modes in a murine model of post-traumatic osteoarthritis","volume":"32","author":"Lockwood","year":"2014","journal-title":"J. Orthop. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/jbmr.3397","article-title":"SOST\/Sclerostin Improves Posttraumatic Osteoarthritis and Inhibits MMP2\/3 Expression After Injury: SOST OVEREXPRESSION IMPROVES PTOA OUTCOMES","volume":"33","author":"Chang","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sebastian, A., Chang, J.C., Mendez, M.E., Murugesh, D.K., Hatsell, S., Economides, A.N., Christiansen, B.A., and Loots, G.G. (2018). Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201808.0244.v1"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sebastian, A., Murugesh, D.K., Mendez, M.E., Hum, N.R., Rios-Arce, N.D., McCool, J.L., Christiansen, B.A., and Loots, G.G. (2020). Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010364"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00383-017-4179-z","article-title":"Characterization of M1 and M2 polarization of macrophages in vascularized human dermo-epidermal skin substitutes in vivo","volume":"34","author":"Klar","year":"2018","journal-title":"Pediatr. Surg. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jaut.2009.09.012","article-title":"Alternatively activated macrophages in infection and autoimmunity","volume":"33","author":"Fairweather","year":"2009","journal-title":"J. Autoimmun."},{"key":"ref_41","unstructured":"Coligan, J.E., Bierer, B.E., Margulies, D.H., Shevach, E.M., and Strober, W. (2011). Quantitative Assessment of Macrophage Functions in Repair and Fibrosis. Current Protocols in Immunology, John Wiley & Sons, Inc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-019-1471-1","article-title":"Locally renewing resident synovial macrophages provide a protective barrier for the joint","volume":"572","author":"Culemann","year":"2019","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-3-319-54090-0_7","article-title":"F4\/80 as a Major Macrophage Marker: The Case of the Peritoneum and Spleen","volume":"62","year":"2017","journal-title":"Results Prob. Cell Differ."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.joca.2019.09.007","article-title":"Complement component C1q is produced by isolated articular chondrocytes","volume":"28","author":"Lubbers","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.molimm.2019.02.013","article-title":"The ficolin response to LPS challenge in mice","volume":"108","author":"Jarlhelt","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s11373-006-9113-7","article-title":"Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis","volume":"13","author":"Lin","year":"2006","journal-title":"J. Biomed. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.3892\/mmr.2015.3790","article-title":"Integrative meta-analysis of differentially expressed genes in osteoarthritis using microarray technology","volume":"12","author":"Wang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.3389\/fimmu.2018.02285","article-title":"BAFF and BAFF-Receptor in B Cell Selection and Survival","volume":"9","author":"Smulski","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jaci.2016.05.036","article-title":"Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency","volume":"139","author":"Bacchelli","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_50","first-page":"1506","article-title":"Increased CD40 expression on articular chondrocytes from patients with rheumatoid arthritis: Contribution to production of cytokines and matrix metalloproteinases","volume":"31","author":"Gotoh","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/art.27292","article-title":"Evidence of epistasis between TNFRSF14 and TNFRSF6B polymorphisms in patients with rheumatoid arthritis","volume":"62","author":"Perdigones","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/art.1780390115","article-title":"The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium","volume":"39","author":"Liu","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7150\/ijms.22345","article-title":"Gene and Protein Expression Profiles in a Mouse Model of Collagen-Induced Arthritis","volume":"15","author":"Gwon","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/art.24293","article-title":"Developmental and osteoarthritic changes in Col6a1-knockout mice: Biomechanics of type VI collagen in the cartilage pericellular matrix","volume":"60","author":"Alexopoulos","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41598-018-36500-2","article-title":"Identification of Chondrocyte Genes and Signaling Pathways in Response to Acute Joint Inflammation","volume":"9","author":"Lv","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"152442","DOI":"10.1016\/j.prp.2019.152442","article-title":"SOX11 promotes osteoarthritis through induction of TNF-\u03b1","volume":"215","author":"Xu","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1016\/j.joca.2018.02.202","article-title":"Loss of Wnt9a and Wnt4 causes degenerative joint alterations","volume":"26","author":"Teufel","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fu, L., Hu, Y., Song, M., Liu, Z., Zhang, W., Yu, F.-X., Wu, J., Wang, S., Izpisua Belmonte, J.C., and Chan, P. (2019). Up-regulation of FOXD1 by YAP alleviates senescence and osteoarthritis. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000201"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.gene.2018.11.068","article-title":"The transcriptional coactivator YAP1 is overexpressed in osteoarthritis and promotes its progression by interacting with Beclin-1","volume":"689","author":"Zhang","year":"2019","journal-title":"Gene"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4049\/jimmunol.1102977","article-title":"TLR5, a novel and unidentified inflammatory mediator in rheumatoid arthritis that correlates with disease activity score and joint TNF-\u03b1 levels","volume":"189","author":"Chamberlain","year":"2012","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41374-019-0345-3","article-title":"CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1\/2 signaling","volume":"100","author":"Zhang","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6002","DOI":"10.1111\/jcmm.13873","article-title":"C5aR1 interacts with TLR2 in osteoblasts and stimulates the osteoclast-inducing chemokine CXCL10","volume":"22","author":"Rapp","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.7150\/thno.15625","article-title":"Role of the CXCL8-CXCR1\/2 Axis in Cancer and Inflammatory Diseases","volume":"7","author":"Ha","year":"2017","journal-title":"Theranostics"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wang, R., Zhang, S., Previn, R., Chen, D., Jin, Y., and Zhou, G. (2018). Role of Forkhead Box O Transcription Factors in Oxidative Stress-Induced Chondrocyte Dysfunction: Possible Therapeutic Target for Osteoarthritis?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123794"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1002\/jbmr.3467","article-title":"Conditional Deletion of Sost in MSC-Derived Lineages Identifies Specific Cell-Type Contributions to Bone Mass and B-Cell Development","volume":"33","author":"Yee","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, R., Yang, X., Wang, J., Han, L., Yang, A., Zhang, J., Zhang, D., Li, B., Li, Z., and Xiong, Y. (2018). Identification of potential biomarkers for differential diagnosis between rheumatoid arthritis and osteoarthritis via integrative genome-wide gene expression profiling analysis. Mol. Med. Rep.","DOI":"10.3892\/mmr.2018.9677"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev.cellbio.12.1.417","article-title":"The mammalian myosin heavy chain gene family","volume":"12","author":"Weiss","year":"1996","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1113\/jphysiol.2009.181008","article-title":"Two novel\/ancient myosins in mammalian skeletal muscles: MYH14\/7b and MYH15 are expressed in extraocular muscles and muscle spindles","volume":"588","author":"Rossi","year":"2010","journal-title":"J. Physiol. (Lond.)"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3233\/JND-160150","article-title":"Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies","volume":"3","author":"Arvanitidis","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.joca.2012.11.016","article-title":"Direct assessment of articular cartilage and underlying subchondral bone reveals a progressive gene expression change in human osteoarthritic knees","volume":"21","author":"Chou","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_71","first-page":"437","article-title":"Differential Expression Patterns of Rspondin Family and Leucine-Rich Repeat-Containing G-Protein Coupled Receptors in Chondrocytes and Osteoblasts","volume":"22","author":"Lee","year":"2021","journal-title":"Cell J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"115269","DOI":"10.1016\/j.bone.2020.115269","article-title":"Post-antibiotic gut dysbiosis-induced trabecular bone loss is dependent on lymphocytes","volume":"134","author":"Schepper","year":"2020","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.4049\/jimmunol.1302998","article-title":"Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in rheumatoid arthritis and experimental arthritis","volume":"193","author":"Kim","year":"2014","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/jor.23263","article-title":"Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis: GLOBAL MOLECULAR CHANGES AFTER ACL INJURY","volume":"35","author":"Chang","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.abb.2014.07.034","article-title":"Bone tissue remodeling and development: Focus on matrix metalloproteinase functions","volume":"561","author":"Paiva","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bone.2016.06.010","article-title":"MMP-13 is one of the critical mediators of the effect of HDAC4 deletion on the skeleton","volume":"90","author":"Nakatani","year":"2016","journal-title":"Bone"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00726-010-0689-x","article-title":"Physiology and pathophysiology of matrix metalloproteases","volume":"41","author":"Klein","year":"2011","journal-title":"Amino Acids"},{"key":"ref_78","first-page":"ME01","article-title":"Ampicillin: Rise fall and resurgence","volume":"8","author":"Kaushik","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.3390\/ijerph110303233","article-title":"Effect of ampicillin, streptomycin, penicillin and tetracycline on metal resistant and non-resistant Staphylococcus aureus","volume":"11","author":"Chudobova","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1172\/JCI102182","article-title":"Neomycin-production and antibiotic properties","volume":"28","author":"Waksman","year":"1949","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/archsurg.1976.01360250098021","article-title":"Neomycin toxicity revisited","volume":"111","author":"Masur","year":"1976","journal-title":"Arch. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1365-2230.1983.tb01777.x","article-title":"Neomycin: A review with particular reference to dermatological usage","volume":"8","author":"Macdonald","year":"1983","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.joca.2015.05.009","article-title":"Non-invasive mouse models of post-traumatic osteoarthritis","volume":"23","author":"Christiansen","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/bja\/53.12.1243","article-title":"Isoflurane","volume":"53","year":"1981","journal-title":"Br. J. Anaesth"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The OARSI histopathology initiative-recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bone.2015.04.048","article-title":"Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model","volume":"82","author":"Yee","year":"2016","journal-title":"Bone"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/17\/6424\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:28Z","timestamp":1760177188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/17\/6424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":86,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21176424"],"URL":"https:\/\/doi.org\/10.3390\/ijms21176424","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,3]]}}}