Related Experiment Videos
The G-protein-coupled receptor GPR103 regulates bone formation
Helene Baribault1, Jean Danao, Jamila Gupte
1Department of Biology Research, Amgen, Mail Stop ASF1-1, 1120 Veterans Blvd., South San Francisco, California 94080, USA. helene@amgen.com
Molecular and Cellular Biology
|December 31, 2005
Summary
Mice lacking G protein-coupled receptor 103 (GPR103) exhibit impaired bone formation, including reduced bone density and kyphosis. These findings suggest GPR103 plays a crucial role in maintaining skeletal integrity.
Area of Science:
- Endocrinology
- Bone Biology
- G protein-coupled receptors
Background:
- G protein-coupled receptor 103 (GPR103) is expressed in various tissues, including the brain and adrenal gland.
- Its natural ligand, 26RFa, is a peptide with orexigenic activity.
- The precise physiological function of GPR103 remains largely unknown.
Purpose of the Study:
- To investigate the role of GPR103 in vivo by generating and analyzing GPR103-deficient mice.
- To elucidate the impact of GPR103 deficiency on bone metabolism and skeletal development.
Main Methods:
- Generation of GPR103 knockout mice (GPR103-/-).
- Histological analysis of bone structure, including osteochondral growth plates and trabecular bone.
- Microcomputed tomography (micro-CT) for detailed bone density assessment.
- Radiography and morphometric analysis to evaluate skeletal abnormalities.
- Reverse transcription-PCR (RT-PCR) to determine GPR103 expression in bone tissues and cell lines.
Main Results:
- GPR103-/- mice displayed a thinned osteochondral growth plate, thickened trabecular branches, and reduced osteoclast numbers.
- Micro-CT revealed decreased trabecular bone and connective tissue densities in GPR103 knockout animals.
- Mutant mice exhibited kyphosis, indicating spinal deformities.
- GPR103 expression was detected in human skull, mouse spine, and osteoblast cell lines.
- Dexamethasone treatment inhibited GPR103 expression in human osteoblast cultures.
Conclusions:
- Loss of GPR103 leads to significant alterations in bone formation and structure, resulting in osteopenia and skeletal deformities.
- GPR103 plays a direct role in regulating osteoblast function and maintaining bone homeostasis.
- These findings highlight GPR103 as a potential therapeutic target for bone-related disorders.
Related Concept Videos
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:40Bone Remodeling
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
01:31Osteoclasts in Bone Remodeling
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:15G Protein-coupled Receptors
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.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...