HUC-MSC secretome and Nanoemulsion Propolis synergistically modulate inflammatory responses in hyperglycemia-induced calvarial osteolysis

Q1 Medicine

Journal of oral biology and craniofacial research Pub Date : 2026-03-01 Epub Date: 2026-03-02 DOI:10.1016/j.jobcr.2026.101430

Putri Cahaya Situmorang , Helen Helen , Syafruddin Ilyas , Salomo Hutahaean , Doni Aldo Samuel Siahaan , Ananto Ali Alhasyimi , Muh Ade Artasasta , Wibi Riawan , Khairul Anuar Shariff , Alexander Patera Nugraha

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引用次数: 0

Abstract

Background

Hyperglycemia-induced osteolysis is a significant consequence of diabetes mellitus, marked by heightened inflammatory responses, augmented osteoclastogenesis, and compromised osteoblast function. Innovative therapy approaches aimed at inflammatory and cytoprotective mechanisms are essential to avert diabetic bone loss.

Objective

This study investigated the synergistic effects of human umbilical cord mesenchymal stem cell (HUC-MSC) secretome and Nanoemulsion Propolis (NEP) on inflammatory responses and protective protein expression in a rat model of hyperglycemia-associated calvarial osteolysis.

Methods

Male Wistar rats were categorized into seven groups: control, LPS-induced inflammation, hyperglycemia, a combination of LPS and hyperglycemia, and treatment groups administered HUC-MSC secretome, NEP, or both. Cytokine concentrations (IL-1β, TNF-α, IL-10) were measured using ELISA, whilst NF-κB, IL-6, HSP-70, and HSP-10 expression in calvarial tissue was assessed by immunohistochemistry.

Results

LPS, in conjunction with hyperglycemia, significantly increased pro-inflammatory cytokines and NF-κB activation, reduced IL-10 levels, and inhibited HSP-70 and HSP-10, hence worsening bone resorption. Treatment with HUC-MSC secretome or NEP alone moderately diminished inflammation, however the combined therapy markedly downregulated NF-κB, IL-1β, TNF-α, and IL-6, while reinstating IL-10 and stress proteins. These modifications diminished osteoclast activation and maintained osteoblast viability, with the most significant protective impact noted in the combination group.

Conclusion

The HUC-MSC secretome and NEP collaboratively influence inflammatory pathways and reinstate protective proteins in calvarial osteolysis triggered by hyperglycemia. This dual technique presents a promising acellular and natural product-based method for addressing diabetes bone loss and associated craniofacial problems.

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HUC-MSC分泌组和纳米乳蜂胶协同调节高血糖诱导的颅骨骨溶解的炎症反应

背景：高血糖诱导的骨溶解是糖尿病的一个重要后果，其特征是炎症反应增强、破骨细胞生成增强和成骨细胞功能受损。针对炎症和细胞保护机制的创新治疗方法对于避免糖尿病骨质流失至关重要。目的研究人脐带间充质干细胞（HUC-MSC）分泌组和纳米乳蜂胶（NEP）对高血糖相关性颅骨骨溶解模型大鼠炎症反应和保护蛋白表达的协同作用。方法将Wistar大鼠分为对照组、LPS诱导炎症组、高血糖组、LPS联合高血糖组和治疗组，分别给予HUC-MSC分泌组、NEP组或两者并用组。ELISA法检测细胞因子（IL-1β、TNF-α、IL-10）浓度，免疫组化法检测颅骨组织中NF-κB、IL-6、热休克蛋白70、热休克蛋白10的表达。结果slps合并高血糖显著增加促炎细胞因子和NF-κB活化，降低IL-10水平，抑制热休克蛋白70和热休克蛋白10，加重骨吸收。单独使用HUC-MSC分泌组或NEP治疗可中度减轻炎症，但联合治疗可显著下调NF-κB、IL-1β、TNF-α和IL-6，同时恢复IL-10和应激蛋白。这些修饰降低了破骨细胞的激活并维持了成骨细胞的活力，在联合组中发现了最显著的保护作用。结论HUC-MSC分泌组和NEP共同影响高血糖引发的颅骨骨溶解的炎症途径和恢复保护蛋白。这种双重技术提出了一种有前途的无细胞和天然产物为基础的方法来解决糖尿病骨质流失和相关的颅面问题。

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来源期刊

Journal of oral biology and craniofacial research Medicine-Otorhinolaryngology

CiteScore

4.90

自引率

0.00%

发文量

133

审稿时长

167 days

期刊介绍： Journal of Oral Biology and Craniofacial Research (JOBCR)is the official journal of the Craniofacial Research Foundation (CRF). The journal aims to provide a common platform for both clinical and translational research and to promote interdisciplinary sciences in craniofacial region. JOBCR publishes content that includes diseases, injuries and defects in the head, neck, face, jaws and the hard and soft tissues of the mouth and jaws and face region; diagnosis and medical management of diseases specific to the orofacial tissues and of oral manifestations of systemic diseases; studies on identifying populations at risk of oral disease or in need of specific care, and comparing regional, environmental, social, and access similarities and differences in dental care between populations; diseases of the mouth and related structures like salivary glands, temporomandibular joints, facial muscles and perioral skin; biomedical engineering, tissue engineering and stem cells. The journal publishes reviews, commentaries, peer-reviewed original research articles, short communication, and case reports.