Targeting RORα in macrophages to boost diabetic bone regeneration

Author:

Shen Yufeng1234,Tang Qingming123,Wang Jiajia123,Zhou Zheng4,Yin Ying123,Zhang Yifan123,Zheng Wenhao123,Wang Xinyuan123,Chen Guangjin123,Sun Jiwei123,Chen Lili123ORCID

Affiliation:

1. Department of Stomatology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022 China

2. School of Stomatology Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030 China

3. Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022 China

4. Department of Stomatology, The First Affiliated Hospital, School of Medicine Shihezi University Shihezi 832000 China

Abstract

AbstractDiabetes mellitus (DM) has become a serious threat to human health. Bone regeneration deficiency and nonunion caused by DM is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Here, we find that targeted activation of retinoic acid‐related orphan receptor α (RORα) by SR1078 in the early stage of bone defect repair can significantly promote in situ bone regeneration of DM rats. Bone regeneration relies on the activation of macrophage RORα in the early bone repair, but RORα of DM rats fails to upregulation as hyperglycemic inflammatory microenvironment induced IGF1‐AMPK signalling deficiency. Mechanistic investigations suggest that RORα is vital for macrophage‐induced migration and proliferation of bone mesenchymal stem cells (BMSCs) via a CCL3/IL‐6 depending manner. In summary, our study identifies RORα expressed in macrophages during the early stage of bone defect repair is crucial for in situ bone regeneration, and offers a novel strategy for bone regeneration therapy and fracture repair in DM patients.

Publisher

Wiley

Subject

Cell Biology,General Medicine

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