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Human periodontal ligament cells (HPDLCs) were used to evaluate the effect of TSG\u20106 on cell function, mitochondrial homeostasis, and the cGAS\u2010STING pathway activation. Human umbilical vein endothelial cells (HUVECs) and mouse bone marrow stem cells (mBMSCs) were employed to further validate TSG\u20106's impact on angiogenesis and osteogenesis under periodontitis microenvironments. C57BL\/6 mice were utilized to establish a ligature\u2010induced periodontitis model. RNA sequencing, quantitative reverse transcription PCR, immunohistochemistry, immunofluorescence staining, enzyme\u2010linked immunosorbent assays, micro\u2010computed tomography, and western blotting were conducted to explore the involvement of TSG\u20106 in periodontitis and its underlying mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The expression of TSG\u20106 was upregulated in the gingival tissues and GCF samples affected by periodontitis compared to that in healthy controls. TSG\u20106 restored cell functions, alleviated inflammation, and promoted osteogenesis in lipopolysaccharide (LPS)\u2010induced HPDLCs via maintaining mitochondrial homeostasis and inhibiting cyclic GMP\u2010AMP synthase (cGAS)\u2010stimulator of interferon genes (STING) pathway activation. Furthermore, local injection of TSG\u20106 effectively suppressed inflammation and attenuated bone resorption while stimulating type H vessel formation and coupled osteoprogenitor expression by reducing CXC\u2010chemokine ligand (CXCL)\u20109 secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TSG\u20106 suppresses inflammation and attenuates bone resorption while stimulating type H vessel formation and coupled bone regeneration in periodontitis via reducing mitochondrial damage, inhibiting cGAS\u2010STING pathway activation, and subsequent CXCL\u20109 secretion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.70120","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:53:40Z","timestamp":1778579620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Necrosis Factor Alpha\u2010Induced Protein 6 Suppresses Inflammation and Promotes Osteogenesis via Type\n                    <scp>H<\/scp>\n                    Vessels in Periodontitis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9899-3074","authenticated-orcid":false,"given":"Yao\u2010Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Periodontology, Shanghai Tongji Stomatological Hospital and Dental School Tongji University  Shanghai P. 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