Human LGR4 (Leucine-rich repeat-containing G-protein coupled receptor 4) ELISA Kit

Tumor necrosis factor (TNF) superfamily member 11 (TNFSF11, also known as RANKL) regulates multiple physiological or pathological functions, including osteoclast differentiation and osteoporosis. TNFRSF11A (also called RANK) is considered to be the sole receptor for RANKL. Herein we report that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL. LGR4 competes with RANK to bind RANKL and suppresses canonical RANK signaling during osteoclast differentiation. RANKL binding to LGR4 activates the G alpha(q) and GSK3-beta signaling pathway, an action that suppresses the expression and activity of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (NFATC1) during osteoclastogenesis. Both whole-body (Lgr4(-/-)) and monocyte conditional knockout mice of Lgr4 (Lgr4 CKO) exhibit osteoclast hyperactivation (including elevation of osteoclast number, surface area, and size) and increased bone erosion. The soluble LGR4 extracellular domain (ECD) binds RANKL and inhibits osteoclast differentiation in vivo. Moreover, LGR4-ECD therapeutically abrogated RANKL-induced bone loss in three mouse models of osteoporosis. Therefore, LGR4 acts as a second RANKL receptor that negatively regulates osteoclast differentiation and bone resorption.

Objective: The transcriptional profile of cumulus cells (CCs) during oocyte maturation provides information for predicting oocyte developmental competence. Our previous study using a mouse model indicated that there were nine different genes related to oocyte development potential expressed in CCs during oocyte maturation. The purpose of this study was to elucidate whether gene expression levels of CCs during oocyte maturation are associated with oocyte developmental competence. Methods: The human CCs collected from each oocyte were divided into two groups after tracking depending on whether or not they developed to the blastocyst stage: (1) the oocytes were developed to blastocyst stage after fertilization (B+) and (2) the oocytes were not developed to blastocyst stage after fertilization (B). The expression levels of the nine selected genes (ARRB1, ATP2C1, CDH5, CNTNAP1, LGR4, MKLN1, RHOBTB1, SIX2, and SMC2) were examined. CCs were obtained from 29 women who were undergoing intracytoplasmic sperm injection treatment cycles. Quantitative reverse transcriptase-polymerase chain reaction analysis was performed on cumulus masses collected before insemination. Each sample was run three times. Statistically significant differences in mRNA expression of the target genes in independent samples were evaluated by two-tailed Student's t-test, and P < 0.05 was considered significantly different. Results: There were significant differences in the mRNA expression levels of ARRB1 (P = 0.016), LGR4 (P = 0.025), and SMC2 (P = 0.013) between the groups B+ and B. Gene expression of ARRB1, LGR4, and SMC2 in CCs is related to blastocyst development. Conclusions: Analysis of expression of ARRB1, LGR4, and SMC2 genes in CCs as biomarkers may provide predictive information on oocyte developmental competence before insemination and fertilization.