ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
This article is part of the Research TopicThe Homeostasis and Perturbations of the Skeletal System and Surrounding EnvironmentView all 8 articles
The Actin Regulator DBNL Is a Critical Mediator of Sympathetic Stress-Induced Bone Loss
Provisionally accepted
- Wuxi Diagnostics, Shanghai, China
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Purpose: Osteoporosis is a prevalent age-associated condition carrying substantial health burdens. The drebrin-like protein (DBNL) has been implicated in regulating communication between osteo-blasts and osteoclasts; however, its function within the sympathetic nervous system (SNS)—an important regulator of bone homeostasis—is not well defined. This study sought to determine whether loss of DBNL alters bone remodeling during sympathetic activation and to elucidate the related molecular pathways. Methods: DBNL knockout (KO) and wild-type (WT) mice were administered isoproterenol (ISO), a β-adrenergic receptor agonist, to simulate SNS activation. Bone microarchitecture was analyzed through micro-computed tomography (micro-CT) and histomorphometry (hematoxylin-eosin and TRAP staining). Bone mechanical properties were evaluated using three-point bending assays. Additionally, chemical sympathectomy via guanethidine was employed to specifically inhibit sympathetic signaling. Quantitative PCR was conducted to assess the expression of genes related to bone formation and resorption. Results: Genetic deletion of DBNL significantly promoted bone formation while suppressing resorptive activity under basal conditions. DBNL-KO mice exhibited intrinsically higher trabecular bone mass compared to WT controls, with significant increases in BMD (p < 0.01) and BV/TV (p < 0.05). ISO administration induced trabecular bone loss in both WT and DBNL-KO mice, as evi-denced by decreased BMD in both genotypes (WT+ISO vs. WT: p < 0.01; KO+ISO vs. KO: p < 0.05). However, DBNL-KO mice maintained higher absolute bone mass values than WT animals after ISO treatment (p < 0.05). DBNL-KO mice also demonstrated preserved mechanical strength under ISO challenge, with significantly higher maximum load compared to WT+ISO group (p < 0.05). Histological evaluation indicated defective preosteoclast fusion and reduced filopodia formation in KO mice. Sympathectomy prevented bone loss in WT controls but not in DBNL-KO mice. 3 Conclusions: Our findings demonstrate that DBNL deficiency elevates basal bone mass and main-tains bone mechanical properties under sympathetic challenge. The preservation of bone mass in DBNL-KO mice during sympathetic activation appears to primarily reflect their intrinsically higher baseline bone mass rather than specific resistance to sympathetic stimulation. DBNL may represent a potential target for modulating bone homeostasis, though further studies are needed to clarify its precise role in SNS-regulated bone metabolism.
Keywords: bone mass, bone metabolism, drebrin-like protein, Sympathetic Nervous System, β-adrenergic
Received: 11 Oct 2025; Accepted: 06 Jan 2026.
Copyright: © 2026 Yin, Gu, Bai, Zhao, Wang, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qin Yin
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