(1) Journal Source
Experimental & Molecular Medicine (2026, Vol. 58, pp. 3565–3578).

(2) Title
Original title: Decreased circulating dopamine β-hydroxylase is associated with medication-related osteonecrosis of the jaw and implicates sympathetic dysregulation.

(3) Research Approach
The study employed unbiased serum proteomics to screen for differentially expressed proteins associated with MRONJ in a discovery cohort, identifying dopamine β-hydroxylase (DBH). The findings were validated in an independent clinical cohort and the large-scale UK Biobank population, and the correlation between DBH levels and blood pressure traits was analyzed. Furthermore, a zoledronic acid-induced mouse MRONJ model and an osteoblast-osteoclast co-culture system were used to investigate the effects of the β-blocker propranolol on jaw osteonecrosis pathology and osteoclast differentiation, thereby evaluating the potential role of sympathetic dysregulation in MRONJ pathogenesis.

(4) Innovation
This study is the first to identify an association between reduced circulating DBH and MRONJ using unbiased proteomics, with validation across multiple populations. It introduces sympathetic nervous system dysregulation into the pathological framework of MRONJ and proposes DBH as a potential circulating biomarker. In vivo and in vitro experiments demonstrate that β-adrenergic signaling inhibition exacerbates zoledronic acid-induced jaw osteonecrosis and exhibits an additive inhibitory effect with bisphosphonates on osteoclast differentiation, providing new evidence for understanding the neuro-skeletal regulation of MRONJ.

(5) Material Development
This article does not involve the development or characterization of new materials, nanomaterials, or delivery systems. The research focuses on proteomic analysis of clinical serum samples, animal model construction, and cell co-culture experiments, which fall under biomarker discovery and pathological mechanism exploration, without material synthesis, carrier construction, or material performance evaluation.

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