{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:12:11Z","timestamp":1779340331781,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The cGAS-STING pathway serves as a key mediator of inflammation. The aim of this study is to explore the biological role and molecular mechanisms of the cGAS-STING pathway in the fracture healing process, with a particular focus on its function during the early inflammatory phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A murine femoral fracture model was utilized to investigate the activation of the cGAS-STING pathway during the early and late stages of bone healing. The methodologies encompassed transcriptome sequencing and immunohistochemistry. Pathway modulation was accomplished through the application of the STING inhibitor H-151 and the activator SR-717, with the effects being assessed via\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments (transcriptome sequencing, microCT, safranin O-fast green staining, and TRAP staining) and\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays (TRAP staining, F-actin ring formation, bone resorption tests, qPCR, and Western blot analysis).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptome analysis revealed a higher expression of STING on day 7 compared to day 21. Immunohistochemistry results also demonstrated significant activation of the cGAS-STING pathway within the fracture callus, particularly during the initial stages of healing. Transcriptome sequencing indicated that the activation of the cGAS-STING pathway by SR-717, in contrast to H-151, predominantly impacted osteoclasts while activating the NF-\u03baB pathway. Results from microCT, safranin O-fast green, and TRAP staining suggested that the activation of the cGAS-STING pathway contributed to facilitating fracture healing and osteoclastogenesis.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments further confirmed that SR-717 enhanced osteoclast formation and activity, while H-151 had an inhibitory effect. The underlying molecular mechanisms further demonstrated that the activation of the cGAS-STING pathway enhanced the transmission of the RANKL-induced NF-\u03baB signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The cGAS-STING pathway played a significant role in the early stages of healing in murine femoral fractures, accelerating the process of fracture repair. This pathway primarily influenced osteoclast differentiation and was associated with the key pathway of osteoclast formation, NF-\u03baB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1789655","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:53:01Z","timestamp":1779339181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["cGAS-STING pathway mediation in osteoclast function and bone fracture healing"],"prefix":"10.3389","volume":"17","author":[{"given":"Miaomiao","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Changhai Hospital, Naval Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shensheng","family":"Nian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Changhai Hospital, Naval Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Changhai Hospital, Naval Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Changhai Hospital, Naval Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Changhai Hospital, Naval Military Medical 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