2. Academic Validation
  3. Maresin1 ameliorates osseointegration in type 2 diabetes mellitus by promoting FAM134B-mediated ER-phagy in osteoblasts

Maresin1 ameliorates osseointegration in type 2 diabetes mellitus by promoting FAM134B-mediated ER-phagy in osteoblasts

  • Biochem Pharmacol. 2025 Oct:240:117099. doi: 10.1016/j.bcp.2025.117099.
Houda Gui 1,  Xi Wang 2,  Ailin Wu 1,  Binyang Li 1,  Bing Zhang 1,  Jiayong Diao 1,  Jingyi Chen 1,  Xi Zhang 1,  Dongni Wu 1,  Qixuan He 1,  Xin Xu 3,  Dongjiao Zhang 4
Affiliations

Affiliations

  • 1 Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
  • 2 Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
  • 3 Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012 Jinan, Shandong, China. Electronic address: xinxu@sdu.edu.cn.
  • 4 Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012 Jinan, Shandong, China. Electronic address: djzhang1109@sdu.edu.cn.
PMID: 40619017 DOI: 10.1016/j.bcp.2025.117099
Abstract

Type 2 diabetes mellitus (T2DM) is a Metabolic Disease characterized by hyperglycemia, the process of implant osseointegration in T2DM patients is severely impaired. The role of endoplasmic reticulum stress (ER stress) and endoplasmic reticulum-phagy (ER-phagy) in this process has been little discussed. Family with sequence similarity 134 member B (FAM134B) is recognized as the most representative ER-phagy receptor and maresin1 is a specialized pro-resolving mediator synthesized by macrophages. In this study, we explored the role of FAM134B-mediated ER-phagy in osseointegration of implants in T2DM. In vitro, we imitated diabetic conditions by using a high-glucose culture medium and altered the expression of FAM134B through genetic manipulation. In vivo, we implanted specialized titanium implants into the femurs of T2DM mice and locally overexpressed FAM134B to investigate the correlation between ER-phagy and osseointegration. We found the high glucose environment impairs implant osseointegration through ER stress, and then ER-phagy acts as an adaptive mechanism, activated in response to ER stress to preserve ER homeostasis and protect cells. Overexpressing FAM134B promoted ER-phagy and alleviated ER stress, thereby rescuing osteogenic disorder and improving osseointegration. Furthermore, maresin1 improved osteogenic function by promoting the FAM134B-mediated ER-phagy. Our study indicated that FAM134B-mediated ER-phagy protects against high-glucose-induced osteogenic disorder and Apoptosis by restoring ER homeostasis. These findings provide support for FAM134B as a promising therapeutic molecular target for improving osseointegration of implants in T2DM patients.

Keywords

ER stress; ER-Phagy; FAM134B; Maresin1; Osseointegration; Type 2 Diabetes Mellitus.

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