{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:51:54Z","timestamp":1781679114891,"version":"3.54.5"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Irreversible pulpitis presents a complex pathological challenge, marked by severe inflammation within the low-compliance dentin chamber. Its progression to pulpal necrosis is governed by intricate molecular interactions. Hyperactivation of the TLR\/NF-\u03baB and MAPK pathways triggers a pro-inflammatory cascade, while HIF-1\u03b1 accumulation under hypoxic conditions induces significant metabolic reprogramming. Meanwhile, the NLRP3 inflammasome exacerbates tissue damage by promoting programmed cell death. Endogenous Wnt\/\u03b2-catenin and TGF-\u03b2\/Smad signaling pathways strive to promote structural repair and dentinogenesis, but are often suppressed by the hyperactive inflammatory environment. Recent translational research highlights the potential of targeted molecular interventions to address this pathological imbalance. This review synthesizes emerging therapeutic strategies aimed at these key pathways, emphasizing the pharmacological use of specific phytochemicals, epigenetic regulators, and specialized pro-resolving mediators, particularly Resolvin E1, which collaboratively attenuate NF-\u03baB-driven inflammation while enhancing Wnt- and TGF-\u03b2-mediated regenerative processes. Additionally, this review discusses the development of next-generation, microenvironment-responsive biomaterials designed to adapt dynamically to pulpal hypoxia and oxidative stress. Ultimately, understanding these signaling interactions lays a molecular foundation for advancing objective, biomarker-based diagnostics and precision therapeutics, offering promising prospects for predictable vital pulp therapy.<\/jats:p>","DOI":"10.3389\/fcell.2026.1872666","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:53:26Z","timestamp":1781675606000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding signaling crosstalk in pulpitis: pathogenesis and precision therapeutics"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhaohui","family":"Jia","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongzong","family":"Sun","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hairui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microecology-immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University","place":["Jiamusi, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jds.2022.06.027","article-title":"Transforming growth factor-\u03b21 promotes early odontoblastic differentiation of dental pulp stem cells via activating AKT, Erk1\/2 and p38 MAPK pathways","volume":"18","author":"Bai","year":"2023","journal-title":"J. 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