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Transducer Mechanism: G Protein–Coupled Receptors01:30

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
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Targeting class A GPCRs for hard tissue regeneration.

So Young Park1, Dohyun Kim2, Ju Won Jung1

  • 1Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea.

Biomaterials
|December 15, 2023
PubMed
Summary

This study identifies G protein-coupled receptors (GPCRs) as targets for regenerating hard tissues like teeth and bone. Drugs targeting specific GPCRs promote mesenchymal stromal cell differentiation, leading to significant tissue repair.

Keywords:
BoneG protein-coupled receptorPulp-dentin complexRegenerative medicine

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Area of Science:

  • Biomedical Science
  • Regenerative Medicine
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are crucial in physiological processes and disease, making them key pharmaceutical targets.
  • Current treatments lack effective strategies for regenerating hard tissues like teeth and bones using GPCR-targeting drugs.
  • Mesenchymal stromal cells (MSCs) possess essential properties for hard tissue regeneration due to their differentiation potential.

Purpose of the Study:

  • To develop a novel strategy for hard tissue regeneration by targeting class A GPCRs.
  • To identify specific class A GPCRs and drug candidates that promote osteogenic and odontogenic differentiation of MSCs.
  • To elucidate the molecular mechanisms underlying GPCR-mediated biomineralization.

Main Methods:

  • In vitro screening of class A GPCRs to identify therapeutic targets and drug candidates.
  • Transcriptome and chromatin accessibility profiling to identify key regulatory factors.
  • In vivo testing of drug efficacy in tooth pulpotomy and calvarial defect models.

Main Results:

  • Six target receptors (LPAR1, F2R, F2RL1, F2RL2, S1PR1, ADORA2A) and effective drug candidates were identified.
  • p53 was identified as a critical transcriptional activator in the biomineralization pathway.
  • Class A GPCR-targeting drugs demonstrated significant regenerative effects in both dental and bone defect models, promoting highly mineralized tissue formation.

Conclusions:

  • Targeting class A GPCRs offers a promising therapeutic approach for hard tissue regeneration.
  • The identified drugs effectively promote MSC differentiation and biomineralization, leading to repair of dental and bone defects.
  • This research provides a translational foundation for developing new regenerative strategies for damaged hard tissues.