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To address this, we used rare human growth plate biopsies obtained from children undergoing epiphysiodesis and exposed them to precisely controlled mechanical loading using a microloading device. The biopsies were cultured 24 hours after mechanical loading, followed by RNA-sequencing analyses to decipher the genomic regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      We conducted RNA-seq analysis of human growth plate cartilage obtained from three patients cultured\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      and subjected to cyclical mechanical loading with peak 0.4 N with frequency 0.77 Hz during a 30-second duration, using a specialized microloading device.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gene ontology analysis revealed novel data showing three significantly upregulated signaling pathways, including notch, oxytocin, and tight junction, and three significantly downregulated signaling pathways, including lysosome, sphingolipid metabolism, and peroxisome proliferator-activated receptor (PPAR) in human growth plate cartilage. Moreover, we found 15 significantly regulated genes within these signaling pathways from all three patients. These genes included PSEN2, HEY1, and NCOR2 from the notch signaling; CACNB1 and PPP3R2 from the oxytocin signaling; ACTR3C, WHAMM, and ARHGEF18 from the tight junction signaling; ARSA, SMPD1, and CD68 from the lysosome signaling; ARSA and SMPD1 from the sphingolipid metabolism signaling; and SLC27A4 and AQP7 from the PPAR signaling pathway. In addition, 20 significantly upregulated genes and six significantly downregulated genes shared between two patient samples were identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides the first-ever transcriptomic data of mechanical loading of human growth plate cartilage. These findings can potentially provide genetic targets for future investigations in physiological and pathological bone growth conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19476035241302954","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:54:55Z","timestamp":1733806495000},"page":"829-844","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genomic Effects of Biomechanical Loading in Adolescent Human Growth Plate Cartilage: A Pilot Study"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9208-4398","authenticated-orcid":false,"given":"Zhengpei","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-8445","authenticated-orcid":false,"given":"Nageswara Rao","family":"Boggavarapu","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynaecology, Department of Women\u2019s and Children\u2019s Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2498-5206","authenticated-orcid":false,"given":"Laila Sara Arroyo","family":"Muhr","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Elimination, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-4053","authenticated-orcid":false,"given":"Ainhoa","family":"Garcia-Serrango","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Elimination, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-4763","authenticated-orcid":false,"given":"Tim RJ","family":"Aeppli","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobia Sebastiano","family":"Nava","sequence":"additional","affiliation":[{"name":"KTH MoveAbility Lab, Department of Engineering Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3002-8296","authenticated-orcid":false,"given":"Yunhan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M.","family":"Gutierrez-Farewik","sequence":"additional","affiliation":[{"name":"KTH MoveAbility Lab, Department of Engineering Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Kulachenko","sequence":"additional","affiliation":[{"name":"Material and Structural Mechanics, Department of Engineering Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"S\u00e4vendahl","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farasat","family":"Zaman","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1302\/2058-5241.5.190088"},{"key":"e_1_3_2_3_2","article-title":"Factors affecting bone growth","volume":"44","author":"Gkiatas I","year":"2015","unstructured":"Gkiatas I, Lykissas M, Kostas-Agnantis I, Korompilias A, Batistatou A, Beris A. 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