{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:04:56Z","timestamp":1785305096074,"version":"3.55.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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. Pharmacol."],"abstract":"<jats:p>The traditional Chinese medicine (TCM) theory of \u201cKidney Governs Bone' has been progressively validated in modern medical research. However, a purely endocrinological perspective cannot fully explain its regulatory implications under complex conditions such as stress, inflammation, and nerve injury. As bone metabolism research shifts toward a systemic regulatory paradigm, the \u201cbrain-bone axis' provides a new framework for reinterpreting \u201cKidney Governs Bone.' Based on current evidence, the core scientific proposition of this article is that we propose the hypothesis that the therapeutic effects of TCM\u2019s \u201cKidney Governs Bone' theory can be partially explained by systemic regulation of the neuro-endocrine-immune network, and that the therapeutic efficacy of TCM interventions may be related to their ability for layered, multi-target regulation within this network. This proposition requires further validation in diverse pathological contexts. Based on this proposition, we propose three conceptual frameworks: \u2460 extending \u201cKidney Governs Bone' from the traditional \u201ckidney-bone' endocrine axis to a systemic regulatory framework centered on the \u201cbrain-bone axis'; \u2461 constructing a three-level \u201ccentral-peripheral-local' regulatory model that systematically integrates the hierarchical interactions within the neuro-endocrine-immune network; and \u2462 proposing a \u201cstratified intervention' strategy for TCM, clarifying the target differences among different therapeutic principles across the three network levels. Using this framework, we systematically evaluate the mechanisms of TCM interventions: kidney-tonifying herbs regulate the hypothalamic-pituitary axis to maintain endocrine homeostasis; kidney-tonifying and blood-activating methods, as well as acupuncture and other external therapies, achieve \u201cneuro-vascular-osteogenic' synergy by modulating sympathetic tone and upregulating neuropeptides such as CGRP; acupuncture and moxibustion remodel the bone immune microenvironment by activating the cholinergic anti-inflammatory pathway, promoting M2 macrophage polarization, and inhibiting NLRP3 inflammasome activation. Current challenges include spatiotemporal heterogeneity, network complexity, and clinical translation gaps. Future studies should employ technologies such as optogenetics, multi-omics integration, and organoid-on-a-chip platforms. The modern scientific connotation of \u201cKidney Governs Bone' is deeply reflected in the systemic regulation of the neuro-endocrine-immune network, and this interdisciplinary direction provides a crucial theoretical breakthrough for transforming TCM orthopedics from empirical medicine toward systems medicine.<\/jats:p>","DOI":"10.3389\/fphar.2026.1862657","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:57:52Z","timestamp":1785304672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A modern reinterpretation of the \u201ckidney governs bone\u201d theory: systemic regulation of the neuro-endocrine-immune network via the brain-bone axis and traditional chinese medicine intervention strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiahao","family":"Dong","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Yunnan University of Chinese Medicine","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Peng","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Hospital of Chinese Medicine","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Hospital of Chinese Medicine","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103006","DOI":"10.1016\/j.brs.2025.103006","article-title":"Subthreshold electric fields bidirectionally modulate neurotransmitter release through axon polarization","volume":"19","author":"Aberra","year":"2026","journal-title":"Brain Stimul."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1177829","DOI":"10.3389\/fphys.2023.1177829","article-title":"Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis","volume":"14","author":"Aguilar","year":"2023","journal-title":"Front. 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