Cannabinoid receptors type 2: Function and development in agonist discovery from synthetic and natural sources with applications for the therapy of osteoporosis
Under a Creative Commons license open access Abstract Type-2 cannabinoid receptor (CB2R) is a member of the G protein-coupled receptor superfamily with various biological activities in pain regulation, anti-inflammation, anti-fibrosis, and bone metabolism regulation. CB2R modulators have been demonstrated to have significant regulatory effects on bone metabolism with no significant psychoactive adverse effects. In this article, we present a comprehensive review of the molecular mechanism of CB2R in regulating bone metabolism and summarize virtual screening and experimental screening methods for CB2R modulators from natural and synthetic products. Knowing that some botanical compounds are CB2R modulators involved in the regulation of bone metabolism, we also review the botanical and synthetic compounds currently known to be potential CB2R and summarize their regulatory effects on bone metabolism based on the results of animal, osteoblasts (OBs) and osteoclasts (OCs) experimental studies presently available, hoping that the findings and conclusions in this review could provide a scientific basis for the discovery of new CB2R regulators and the development of new anti-osteoporosis drugs. Keywords Cannabinoid receptors type 2 Osteoporosis CB2R agonist discovery Osteoblasts Osteoclasts Abbreviations NF-κB nuclear factor kappa-B PKA protein kinase A ERK1/2 extracellular signal-regulated protein kinase 1/2 JNK c-Jun N-terminal kinase cAMP cyclic adenosine monophosphate c-Fos cellular oncogene fos c-JUN Jun activation domain binding protein AP1 activator protein-1 IκBα inhibitor α of NF-κB MMP-9 matrix metalloproteinase-9 PI3K phosphatidylinositol 3-kinase p-AKT phosphate protein kinases B PKC protein kinase C DAG diacylglycerol NFATc1 nuclear factor of activated T-cells, cytoplasmic 1 CREB cAMP-response element binding protein Cox cyclooxygenase ATP adenosine-triphosphate FAK focal adhesion kinase Src strict-regime camps RhoA ras homolog gene family, member A TCF/LEF ternary complex factor/lymphoid enhancing factor OCN osteocalcin ALP alkaline phosphatase OPG recombinant osteoprotegerin Runx2 recombinant runt related transcription factor 2 p38 cell signaling protein p52 proteins that play an important role in adhesion of eukaryotic cells p65 a marker of NF-κB pathway activation Cited by (0) © 2023 The Author(s).
Tags:
- Cannabinoid receptor 2
- NF-κB
- Kinase
- Cyclic adenosine monophosphate
- Protein kinase A
- Protein c-Fos
- Protein kinase
- AP-1 transcription factor
- Transcription factor Jun
- Protein kinase C
- PTK2
- Bone
- Transforming protein RhoA
- Human biology
- Human genes
- Proteins
- Biotechnology
- Nutrients
- Biology
- Molecular biology
- Neurochemistry
- Cellular processes
- Cell communication
- Signal transduction
- Biochemistry
- Cell signaling
- Cell biology
- Mammal genes