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β-淀粉样肽治疗通过Wnt信号通路逆转下颌髁突骨质流失。

Amyloid-β peptide treatment reverses bone loss in the mandibular condyle via Wnt signalling pathway.

作者信息

Chen Qiang, Tu Shaoqin, Tang Dongxiao, Wei Jiaming, Wei Nan, Ai Hong, Yang Bu, Chen Zheng

机构信息

Department of Stomatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Spine Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Bone Rep. 2024 Jul 8;22:101788. doi: 10.1016/j.bonr.2024.101788. eCollection 2024 Sep.

Abstract

OBJECTIVE

To explore the effect of amyloid-β peptide (Aβ) on mandibular condyle to develop a new treatment for postmenopausal women with Temporomandibular joint osteoarthritis.

METHODS

A murine bone loss model was established by ovariectomy. Microstructure parameters of the condyle were measured by microcomputed tomography before and after intraperitoneal injection with Aβ. Flow cytometry, Alizarin red staining, RT-qPCR assays, FITC/PI staining, Oil Red O staining and western blotting were used to evaluate the effect of Aβ on the osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs).

RESULTS

In vivo, condylar microstructure parameters increased. Serum osteoprotegerin and procollagen type 1 N propeptide increased in a dose-dependent manner after the injection of Aβ, which were opposite the changes observed in c-terminal telopeptides of type I collagen, tumor necrosis factor-α and the high serum level of leptin. In vitro, Aβ promoted calcium nodule formation in the cells. The expression of ALP, Runx2, osteorix and osteocalcin increased significantly. The expression of mRNAs related to the Wnt signaling pathway was significantly upregulated, which could be blocked by DKK1.

CONCLUSION

Aβ can reverse bone loss in the mandibular condyle in ovariectomized mice through promoting the osteogenic differentiation of mBMSCs via the Wnt pathway.

摘要

目的

探讨β淀粉样蛋白(Aβ)对下颌髁突的影响,为绝经后颞下颌关节骨关节炎女性开发新的治疗方法。

方法

通过卵巢切除术建立小鼠骨质流失模型。在腹腔注射Aβ前后,用微型计算机断层扫描测量髁突的微观结构参数。采用流式细胞术、茜素红染色、RT-qPCR检测、FITC/PI染色、油红O染色和蛋白质印迹法评估Aβ对小鼠骨髓间充质干细胞(mBMSC)成骨分化的影响。

结果

在体内,髁突微观结构参数增加。注射Aβ后,血清骨保护素和I型前胶原N端前肽呈剂量依赖性增加,这与I型胶原C端肽、肿瘤坏死因子-α和高血清瘦素水平的变化相反。在体外,Aβ促进细胞中钙结节的形成。碱性磷酸酶、Runx2、osteorix和骨钙素的表达显著增加。与Wnt信号通路相关的mRNA表达显著上调,这可被DKK1阻断。

结论

Aβ可通过Wnt途径促进mBMSC的成骨分化,从而逆转去卵巢小鼠下颌髁突的骨质流失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3483/11301219/ba1e47346cec/gr1.jpg

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