{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:44:32Z","timestamp":1788799472652,"version":"build-2803163510"},"reference-count":41,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Hydrogen sulfide (H2S) plays an essential role in bone formation, in part, by inhibiting osteoclast differentiation, maintaining mesenchymal stem cell osteogenesis ability, or reducing osteoblast injury. We aimed to investigate the role of H2S in osteoblast function and its possible molecular target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In this study, we found that cystathionine \u03b3-lyase (CSE) majorly contributed to endogenous H2S production in the primary osteoblast. Overexpressed CSE increased osteoblast differentiation and maturation with higher bone morphogenetic protein 2 and osteopontin expression, alkaline phosphatase activity, and calcium nodule formation; in contrast, knockdown of CSE had opposite effects. Runt-related transcript factor 2 (RUNX2) is required for osteoblast biologic function. CSE-H2S increased nuclear RUNX2 accumulation, DNA binding activity, and target gene transcription. Protein sulfhydration is a common signal by H2S. We confirmed that RUNX2 was also sulfhydrated by H2S. This chemical modification enhanced RUNX2 transactivation, which was blocked by dithiothreitol (DTT, sulfhydration remover). Mutation of two cysteine sites in the runt domain of RUNX2 abolished H2S-induced RUNX2 sulfhydration and transactivation. In a bone -fracture rat model, overexpressed CSE promoted bone healing, which confirmed the effect of CSE-H2S on osteoblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>CSE-H2S is a dominant H2S generation system in osteoblasts and promotes osteoblast activity by the RUNX2 pathway, with RUNX2 sulfhydration as a novel transactivation regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      CSE-H2S sulfhydrated RUNX2 enhanced its transactivation and increased osteoblast differentiation and maturation, thereby promoting bone healing.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                      . 27, 742\u2013753.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2016.6826","type":"journal-article","created":{"date-parts":[[2017,2,4]],"date-time":"2017-02-04T01:41:02Z","timestamp":1486172462000},"page":"742-753","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":60,"title":["Cystathionine \u03b3-Lyase\u2013Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing"],"prefix":"10.1177","volume":"27","author":[{"given":"Yang","family":"Zheng","sequence":"first","affiliation":[{"name":"National Center for Cardiovascular Diseases","place":["China"]},{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liao","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center","place":["China"]},{"name":"Sichuan Provincial People's Hospital, Chengdu","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianjuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Fan","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Cui","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Yang","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Geng","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases","place":["China"]},{"name":"Peking University Health Science Center","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cai","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,10,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020216"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408742102"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v028a19"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-015-0270-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.03.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.05.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-015-0404-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.4.1858"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80257-3"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199404000-00008"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2014.06.014"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2757"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3945\/jn.113.187922"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512494200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2014.11.012"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-004-0072-x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700030200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2741\/2730"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22994"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80258-5"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.23.8783-8792.2000"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24461"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2013.08.004"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep16590"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.03.005"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000464"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-415-5_3"},{"key":"e_1_3_3_30_2","first-page":"57","article-title":"Bone injury and fracture healing biology","volume":"28","author":"Oryan A","year":"2015","unstructured":"Oryan A, , Monazzah S, , and Bigham-Sadegh A. Bone injury and fracture healing biology. Biomed Environ Sci, 28: 57\u201371, 2015.","journal-title":"Biomed Environ Sci"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80259-7"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.08.007"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25604"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1750-3"},{"key":"e_1_3_3_35_2","first-page":"117","article-title":"Hydrogen sulfide and sodium nitroprusside compete to activate\/deactivate MMPs in bone tissue homogenates","volume":"9","author":"Vacek TP","year":"2013","unstructured":"Vacek TP, , Qipshidze N, , and Tyagi SC. Hydrogen sulfide and sodium nitroprusside compete to activate\/deactivate MMPs in bone tissue homogenates. Vasc Health Risk Manag, 9: 117\u2013123, 2013.","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032546"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2015.04.008"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2011"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2006.00283.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.02.016"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.3.681"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.212"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ars.2016.6826","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2016.6826","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2016.6826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:54:23Z","timestamp":1777377263000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/ars.2016.6826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1089\/ars.2016.6826"],"URL":"https:\/\/doi.org\/10.1089\/ars.2016.6826","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]}}}