scholarly journals Type B γ-Aminobutyric Acid Receptors Modulate the Function of the Extracellular Ca2+-Sensing Receptor and Cell Differentiation in Murine Growth Plate Chondrocytes

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4984-4992 ◽  
Author(s):  
Zhiqiang Cheng ◽  
Chialing Tu ◽  
Luis Rodriguez ◽  
Tsui-Hua Chen ◽  
Melita M. Dvorak ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Growth Plate ◽  
Type Ii Collagen ◽  
Aminobutyric Acid ◽  
Physical Interaction ◽  
Type B ◽  
Growth Plate Chondrocytes ◽  
Differentiation Markers ◽  
Receptor Complexes

Extracellular calcium-sensing receptors (CaRs) and metabotropic or type B γ-aminobutyric acid receptors (GABA-B-Rs), two closely related members of family C of the G protein-coupled receptor superfamily, dimerize in the formation of signaling and membrane-anchored receptor complexes. We tested whether CaRs and two GABA-B-R subunits (R1 and R2) are expressed in mouse growth plate chondrocytes (GPCs) by PCR and immunocytochemistry and whether interactions between these receptors influence the expression and function of the CaR and extracellular Ca2+-mediated cell differentiation. Both CaRs and the GABA-B-R1 and -R2 were expressed in the same zones of the growth plate and extensively colocalized in intracellular compartments and on the membranes of cultured GPCs. The GABA-B-R1 coimmunoprecipitated with the CaR, confirming a physical interaction between the two receptors in GPCs. In vitro knockout of GABA-B-R1 genes, using a Cre-lox recombination strategy, blunted the ability of high extracellular Ca2+ concentration to activate phospholipase C and ERK1/2, suppressed cell proliferation, and enhanced apoptosis in cultured GPCs. In GPCs, in which the GABA-B-R1 was acutely knocked down, there was reduced expression of early chondrocyte markers, aggrecan and type II collagen, and increased expression of the late differentiation markers, type X collagen and osteopontin. These results support the idea that physical interactions between CaRs and GABA-B-R1s modulate the growth and differentiation of GPCs, potentially by altering the function of CaRs.

scholarly journals Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

2002 ◽  
Vol 50 (8) ◽  
pp. 1059-1065 ◽  
Author(s):  
Sherri R. Davies ◽  
Shinji Sakano ◽  
Yong Zhu ◽  
Linda J. Sandell
Keyword(s):  
Transcription Factors ◽  
Growth Plate ◽  
Type Ii Collagen ◽  
Nuclear Staining ◽  
Lower Growth ◽  
Biological Studies ◽  
Transcription In Vitro ◽  
Sox9 Protein

The control of extracellular matrix (ECM) production is important for the development, maintenance, and repair of cartilage tissues. Matrix molecule synthesis is generally regulated by the rate of gene transcription determined by DNA transcription factors. We have shown that transcription factors Sox9, AP-2, and [delta]EF1 are able to alter the rate of CD-RAP transcription in vitro: Sox9 upregulates, AP-2 exhibits biphasic effects, and [delta]EF1 represses expression of the CD-RAP gene. To correlate these in vitro activities in vivo, transcription factors were co-immunolocalized with ECM proteins in three different cartilage tissues in which the rates of biosynthesis are quite different: articular, meniscal, and growth plate. Immunoreactivities of type II collagen and CD-RAP were higher in growth plate than in either the articular or meniscal cartilages and correlated positively with Sox9 protein. Sox9 staining decreased with hypertrophy and was low in articular and meniscal cartilages. In contrast, AP-2 and [delta]EF1 were low in proliferating chondrocytes but high in lower growth plate, articular, and meniscal cartilages. This increase was also accompanied by intense nuclear staining. These immunohistochemical results are the first to localize both [delta]EF1 and AP-2 to adult articular, meniscal, and growth plate cartilages and provide in vivo correlation of previous molecular biological studies.

HiPER1, a phosphatase of the endoplasmic reticulum with a role in chondrocyte maturation

1998 ◽  
Vol 111 (6) ◽  
pp. 803-813
Author(s):  
P.R. Romano ◽  
J. Wang ◽  
R.J. O'Keefe ◽  
J.E. Puzas ◽  
R.N. Rosier ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Growth Plate ◽  
Articular Chondrocytes ◽  
Signal Sequence ◽  
Growth Plate Chondrocytes ◽  
Chondrocyte Maturation ◽  
Er Retention ◽  
Alternatively Spliced ◽  
Dual Label

We have previously identified and partially cloned Band 17, a gene expressed in growth plate chondrocytes transiting from proliferation to hypertrophy. We now rename this gene HiPER1, Histidine Phosphatase of the Endoplasmic Reticulum-1, based on the results reported here. HiPER1 encodes two proteins of 318 (HiPER1(318)) and 449 (HiPER1(449)) amino acids, which are 20–21% identical to a group of yeast acid phosphatases that are in the histidine phosphatase family. HiPER1(449) is significantly more abundant than HiPER1(318), correlating with the abundance of the alternatively spliced messages encoding HiPER449 and HiPER318. Anti-HiPER1 antibodies detect two proteins of 53 and 55 kDa in growth plate chondrocytes that are absent in articular chondrocytes. We confirm that the 53 and 55 kDa proteins are HiPER1(449) by heterologous expression of the HiPER1(449) coding sequence in chick embryo fibroblasts. The 53 and 55 kDa proteins are glycosylated forms of HiPER1(449), as N-glycosidase F digestion reduces these proteins to 48 kDa, the predicted size of HiPER1(449) without the N-terminal signal sequence. Immunocytochemistry demonstrates that HiPER1(449) is found in chondrocytes maturing from proliferation to hypertrophy, but is not detectable in resting zone, deep hypertrophic zone or articular chondrocytes, a distribution that is consistent with the message distribution. HiPER1(449) was predicted to localize to the lumen of endoplasmic reticulum by an N-terminal signal sequence and by the C-terminal sequence Ala-Asp-Glu-Leu, which closely matches the consensus signal for ER retention, Lys-Asp-Glu-Leu. We confirm this prediction by demonstrating colocalization of HiPER1(449) with the ER protein HSP47 using dual-label immunofluorescence. PTHrP, a peptide that prevents hypertrophy in chondrocytes, suppressed HiPER1 and HiPER1(449) expression in vitro, an observation that further supports a role for HiPER1 in chondrocyte maturation. The yeast phosphatase homology, localization to the endoplasmic reticulum and pattern of expression suggest that HiPER1 represents a previously unrecognized intracellular pathway, involved in differentiation of chondrocytes.

scholarly journals Parathyroid hormone prevents 1,25(OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro

1997 ◽  
Vol 52 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Günter Klaus ◽  
Tanja May ◽  
Ulrike Hügel ◽  
Barbara Von Eichel ◽  
Julian Rodriguez ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Plate ◽  
Vitamin D Receptor ◽  
Growth Plate Chondrocytes ◽  
Down Regulation

scholarly journals Potential ligand-receptor-pathway cascades and a novel non-metabolic function of lactate in remodeling uterine receptivity by inducing endometrial histone lactylation at implantation, revealed by a proteomic atlas of maternal-fetal crosstalk

2021 ◽  
Author(s):  
Qianying Yang ◽  
Juan Liu ◽  
Yue Wang ◽  
Wei Zhao ◽  
Wenjing Wang ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Redox Homeostasis ◽  
Integrated Analysis ◽  
Physical Interaction ◽  
Metabolic Function ◽  
Uterine Receptivity ◽  
Cellular Mechanisms ◽  
Receptor Complexes

Abstract Well-orchestrated maternal-fetal crosstalk involves secreted ligands, interacting receptors, and coupled pathways between the conceptus and endometrium. However, previous researches mainly focused on either the conceptus or endometrium in isolation. The lack of integrated analysis, especially on protein levels, has made it challenging to advance our understanding of the crosstalk. Herein, focusing on ligand–receptor complexes and coupled pathways at maternal-fetal interface in sheep, a well-established embryo implantation model, we provide the first comprehensive proteomic atlas of ligand-receptor-pathway cascades that may be essential for implantation. Based on these candidate interactions, we further revealed the physical interaction of albumin-claudin 4 and their role in facilitating embryo attachment to endometrium. More interestingly, we demonstrated a novel non-metabolic function of enhanced conceptus glycolysis in remodeling uterine receptivity, by inducing endometrial histone lactylation, a newly identified histone modification. Our results from in vitro and in vivo models supported the essential role of lactate, as a key embryonic signal, in regulating redox homeostasis and apoptotic balance to ensure successful implantation. Our study identified many putative molecular and cellular mechanisms that fine-tuned conceptus-endometrium crosstalk during implantation, thus providing important clues for developing potential clinical intervention strategies to improve pregnancy outcomes following both natural conception and assisted reproduction.

scholarly journals A novel C-type lectin regulating cell growth, cell adhesion and cell differentiation of the multipotent epithelium in budding tunicates

Development ◽  
2001 ◽  
Vol 128 (17) ◽  
pp. 3339-3347 ◽  
Author(s):  
Jun Matsumoto ◽  
Chiaki Nakamoto ◽  
Shigeki Fujiwara ◽  
Toshitsugu Yubisui ◽  
Kazuo Kawamura
Keyword(s):  
Cell Adhesion ◽  
Cell Differentiation ◽  
Cell Growth ◽  
Cell Aggregation ◽  
Amino Acid Sequences ◽  
The Other ◽  
Differentiation Markers ◽  
Multipotent Cells ◽  
Epithelial Origin

We have isolated two Ca2+-dependent, galactose-binding polypeptides from the budding tunicate, Polyandrocarpa misakiensis. Based on their partial amino acid sequences, full-length cDNAs were cloned. One of them was identical with a tunicate C-type lectin (TC14-2) reported previously. The other was a novel C-type lectin, referred to as TC14-3. In living animals, they appeared to be coupled. This complex of lectins, when applied in vitro to tunicate multipotent cells of epithelial origin, blocked cell proliferation and induced cell aggregation. The aggregates expressed a homolog of the integrin α-chain and other differentiation markers specific for epithelial cells. Recombinant TC14-3 could reproduce all the activities of native lectins by itself, which was accelerated by recombinant TC14-2. The inhibitory activity of TC14-3 on cell growth was completely abolished by the addition of 50 μM D-galactose. Anti-TC14-3 monoclonal antibody showed that the antigen was expressed constitutively by the multipotent epithelial and mesenchymal cells. These results provide evidence that in P. misakiensis a C-type lectin plays a novel, cytostatic role in regulating cell growth, cell adhesion and cell differentiation during asexual reproduction.

scholarly journals A proteomic atlas of ligand-receptor interactions at the ovine maternal-fetal interface reveals the role of histone lactylation in uterine remodeling

2021 ◽  
Author(s):  
Qianying Yang ◽  
Juan Liu ◽  
Yue Wang ◽  
Wei Zhao ◽  
Wenjing Wang ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Redox Homeostasis ◽  
Integrated Analysis ◽  
Physical Interaction ◽  
Uterine Receptivity ◽  
In Vivo Models ◽  
Receptor Complexes ◽  
Maternal Fetal Interface

Abstract Well-orchestrated maternal-fetal crosstalk occurs via secreted ligands, interacting receptors, and coupled intracellular pathways between the conceptus and endometrium, and is essential for successful embryo implantation. However, previous studies mostly focus on either the conceptus or the endometrium in isolation. The lack of integrated analysis impedes our understanding of early maternal-fetal crosstalk. Herein, focusing on ligand–receptor complexes and coupled pathways at the maternal-fetal interface in sheep, we provide the first comprehensive proteomic map of ligand-receptor pathway cascades essential for embryo implantation. We demonstrate that these cascades are associated with cell adhesion and invasion, redox homeostasis, and the immune response. Candidate interactions and their physiological roles were further validated by functional experiments. We reveal the physical interaction of albumin and claudin 4 and their roles in facilitating embryo attachment to endometrium. We also demonstrate a novel function of enhanced conceptus glycolysis in remodeling uterine receptivity by inducing endometrial histone lactylation, a newly identified histone modification. Results from in vitro and in vivo models supported the essential role of lactate in inducing endometrial H3K18 lactylation and in regulating redox homeostasis and apoptotic balance to ensure successful implantation. By reconstructing a map of potential ligand-receptor pathway cascades at the maternal-fetal interface, our study presents new concepts for understanding molecular and cellular mechanisms that fine-tune conceptus-endometrium crosstalk during implantation. This provides more direct and accurate insights for developing potential clinical intervention strategies to improve pregnancy outcomes following both natural and assisted conception.

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