이순철 (차의과학대학교)

한빛사논문

조회372

이순철Soonchul Lee

차의과학대학교

Biomaterials, Volume 304, January 2024, 122425 | https://doi.org/10.1016/j.biomaterials.2023.122425 Targeting class A GPCRs for hard tissue regeneration

So Young Park ^a,1, Dohyun Kim ^b,1, Ju Won Jung ^a,2, Hyun-Ju An ^c, Jaemin Lee ^c, Yeji Park ^b, Dasun Lee ^b, Soonchul Lee ^c, Jin Man Kim^a

^aDepartment of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea

^bDepartment of Conservative Dentistry and Oral Science Research Center, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea

^cDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Bundang-gu, Seongnam-si, 13496, Republic of Korea

¹These authors contributed equally to this work.

²Current address: Department and Research Institute of Dental Biomaterials and Bioengineering, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea.

Corresponding authors: Soonchul Lee, Jin Man Kim

Abstract

G protein-coupled receptors (GPCRs) play important roles in various pathogeneses and physiological regulations. Owing to their functional diversity, GPCRs are considered one of the primary pharmaceutical targets. However, drugs targeting GPCRs have not been developed yet to regenerate hard tissues such as teeth and bones. Mesenchymal stromal cells (MSCs) have high proliferation and multi-lineage differentiation potential, which are essential for hard tissue regeneration. Here, we present a strategy for targeting class A GPCRs for hard tissue regeneration by promoting the differentiation of endogenous MSCs into osteogenic and odontogenic progenitor cells. Through in vitro screening targeted at class A GPCRs, we identified six target receptors (LPAR1, F2R, F2RL1, F2RL2, S1PR1, and ADORA2A) and candidate drugs with potent biomineralization effects. Through a combination of profiling whole transcriptome and accessible chromatin regions, we identified that p53 acts as a key transcriptional activator of genes that modulate the biomineralization process. Moreover, the therapeutic potential of class A GPCR-targeting drugs was demonstrated in tooth pulpotomy and calvarial defect models. The selected drugs revealed potent regenerative effects in both tooth and bone defects, represented by newly formed highly mineralized regions. Consequently, this study provides translational evidence for a new regenerative strategy for damaged hard tissue.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2023-12-18)
연구진국내 연구진
분야 생명과학 > 분자생물학

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