Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
[Backgrounds]
It is known that various receptors are expressed on osteoblasts and their physiological functions are being elucidated. We determined expression levels of opioid receptors and found that opioid growth factor receptor (OGFR) is strongly expressed in osteoblasts compared to canonical opioid receptors (mu-, kappa-, delta-opioid receptors). OGFR differs in structure and function from canonical opioid receptors and is localized around the nucleus. It has been reported that OGFR is involved in cell proliferation in various cancer cells. However, little is known about the physiological role in osteoblasts. In this study, we examined the physiological role of OGFR signaling in osteoblasts by in vitro and in vivo experiments.
[Methods]
MC3T3-E1 osteoblast-like cells were used in vitro. In the presence and absence of methionine-enkephalin (Met-enk) which is an agonist of OGFR, cell proliferation activity was measured by the WST method. The expression levels of the cell proliferation-related genes were analyzed by quantitative real-time PCR method.
In vivo experiment, naltrexone (NTX) (0.1 mg/kg, 1 mg/kg) was intraperitoneally administered to 7-week old ICR male mice for 28 days, and the control group received saline. After the administration, micro CT analysis of the femur and analysis of bone morphology measurement of the tibia were performed.
[Results]
Met-enk increased the expression level of p21 gene and suppressed cell proliferation in MC3T3-E1 cells. On the other hand, cell proliferation tended to be promoted by NTX treatment. Administration of NTX (0.1 mg/kg) to mice for 28 days significantly increased the BV/TV (bone volume/tissue volume) value compared to the control group. Moreover, a significant increase in Ob.N/BS (osteoblasts number/bone surface) and BFR (bone formation rate) was observed in NTX administration group.
[Discussion]
These results suggested that blocking of OGFR signaling may contribute to increase of bone mass through promotion of cell proliferation in osteoblasts.
