Effect of S1P/S1PR on bone metabolism in bisphosphonate-related osteonecrosis of the jaws.

Ting Guo, Yuhao Wang, Dianri Wang, Wenbin Yang, Xiye Sun, Jiyuan Liu, Jian Pan

Abstract read

In one paragraph

Article in Medical molecular morphology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Ting Guo *State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, #14 Third Section, Renmin Road South, Chengdu, 610041, Sichuan, China.

Yuhao Wang *State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, #14 Third Section, Renmin Road South, Chengdu, 610041, Sichuan, China.

Dianri WangState Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, #14 Third Section, Renmin Road South, Chengdu, 610041, Sichuan, China.

Wenbin YangState Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, #14 Third Section, Renmin Road South, Chengdu, 610041, Sichuan, China.

Xiye SunDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia.

Jiyuan LiuState Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, #14 Third Section, Renmin Road South, Chengdu, 610041, Sichuan, China. 20532465@qq.com.

Jian PanState Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, #14 Third Section, Renmin Road South, Chengdu, 610041, Sichuan, China. jianpancn@scu.edu.cn.ORCID http://orcid.org/0000-0003-1346-048X

Funding

Science and Technology Department of Sichuan Province No. 2023ZYD0110West China School of Stomatology, Sichuan University No. RD-03-202405

6 · The paper itself

Abstract

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a major adverse effect of bisphosphonates, yet its underlying pathogenesis remains poorly understood. Bone metabolism and remodeling relies on the interaction between osteoblasts (OBs) and osteoclasts (OCs). Sphingosine 1-phosphate (S1P), a bioactive sphingolipid metabolite, is an important mediator of OC-OB communication. In this study, we aimed to investigate the role of the S1P/S1P receptor (S1PR) axis in the development of BRONJ. A co-culture system was used to examine the interaction between OCs and OBs. Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of related proteins and messenger ribonucleic acids (mRNAs). Finally, an in vivo BRONJ mouse model was used to validate the role of S1P/S1PR axis in disease progression. In our study, we showed that zoledronate (ZOL) promoted S1P secretion from OCs and enhanced the migration of osteoclast precursor cells (OCPs) through S1PR signaling. In addition, OCs promoted the excessive osteogenic differentiation and migration of OBs via S1P/S1PR axis. Importantly, pharmacological inhibition of S1PR facilitated the recovery of BRONJ-like lesions in vivo. In conclusion, these findings indicate that the S1P/S1PR axis plays an important role in the pathogenesis of BRONJ and may represent a potential therapeutic target for its treatment.

Indexed as

Bisphosphonate-Associated Osteonecrosis of the JawBone and BonesLysophospholipidsReceptors, LysosphingolipidSphingosineSphingosine-1-Phosphate ReceptorsAnimalsCell DifferentiationCell MovementCoculture TechniquesDiphosphonatesDisease Models, AnimalHumansMiceOsteoblastsOsteoclastsDiphosphonatesLysophospholipidsReceptors, LysosphingolipidSphingosinesphingosine 1-phosphateSphingosine-1-Phosphate ReceptorsZoledronic AcidAutocrine/paracrineBisphosphonate-related osteonecrosis of the jawsBone metabolismSphingosine-1-phosphateZoledronate

Identifiers

PMID42029939

DOI10.1007/s00795-026-00461-7

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.