Orai1–Orai2 complex is involved in store-operated calcium entry in chondrocyte cell lines

Inayama, Munenori; Imaizumi, Yuji; Yamada, Satoshi; Kurita, Takashi; Yamamura, Hisao; Ohya, Susumu; Giles, Wayne R.; Imaizumi, Yuji

doi:10.1016/j.ceca.2015.02.005

Cited by 41 publications

(53 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We further show that the known TRPC6 activator hyperforin (Hyp) (Leuner et al, 2007) and a novel nSOC-positive modulator, NSN21778 (NSN) (Wu et al, 2011), can stimulate STIM2-nSOC pathway in the spines and rescue mushroom spine loss in both PS1KI mice (Guo et al, 1999) and APP NL-F/NL-F knock-in mice (APPKI) mice (Saito et al, 2014) hippocampal neurons. Furthermore, we demonstrate that NSN rescues hippocampal long-term potentiation (LTP) impairment in APPKI mice.…”

Section: Introductionmentioning

confidence: 90%

“…The PS1-M146V knock-in mice (PS1KI) (Guo et al, 1999) were kindly provided by Hui Zheng (Baylor University). APPKI mice were kindly provided by Takaomi Saido (Riken, Japan) (Saito et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

“…Wild-type (WT) mice of the same strain (C57BL/6) were used in control experiments. PS1KIGFP and APPKIGFP mice were generated by crossing PS1KI or APPKI mice with Line M GFP mice (C57BL/6 strain) (Feng et al, 2000). All mice colonies were established and housed in a vivarium (four per cage) with 12 h light/dark cycle at the University of Texas (UT) Southwestern Medical Center barrier facility.…”

Section: Methodsmentioning

confidence: 99%

“…To analyze the shape of the spines in hippocampus in vivo, we used the GFP-M mouse line (Feng et al, 2000) (WTGFP). To simplify the analysis, we crossed Line M GFP mice with PS1KI and APPKI mice to yield PS1KIGFP and APPKIGFP mice.…”

Section: Quantitative Reverse Transcription Pcr (Qrt-pcr)mentioning

confidence: 99%

“…There are six TRPC proteins in humans (TRPC1 and TRPC3-TRPC7), which have been divided into two subfamilies, TRPC1/TRPC4/TRPC5 and TRPC3/TRPC6/TRPC7, based on biochemical and functional similarities. The remaining member, TRPC2, is a pseudogene in humans but is expressed in other species in a restricted expression pattern (Cheng et al, 2013). There are three Orai channels (Orai1-Orai3) but, so far, most studies have been focused on Orai1.…”

Section: Trpc6 and Orai2 Support Stim2-gated Nsoc In Hippocampal Mushmentioning

confidence: 99%

See 4 more Smart Citations

Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment

et al. 2016

View full text Add to dashboard Cite

Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca 2ϩ influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca 2ϩ channel complex in hippocampal mushroom spines. We further demonstrate that a known TRPC6 activator, hyperforin, and a novel nSOC positive modulator, NSN21778 (NSN), can stimulate activity of nSOC pathway in the spines and rescue mushroom spine loss in both presenilin and APP knock-in mouse models of AD. We further show that NSN rescues hippocampal long-term potentiation impairment in APP knock-in mouse model. We conclude that the STIM2-regulated TRPC6/Orai2 nSOC channel complex in dendritic mushroom spines is a new therapeutic target for the treatment of memory loss in aging and AD and that NSN is a potential candidate molecule for therapeutic intervention in brain aging and AD.

show abstract

Section: Introductionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Quantitative Reverse Transcription Pcr (Qrt-pcr)mentioning

confidence: 99%

Section: Trpc6 and Orai2 Support Stim2-gated Nsoc In Hippocampal Mushmentioning

confidence: 99%

See 3 more Smart Citations

Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment

et al. 2016

View full text Add to dashboard Cite

show abstract

Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism

Gong

Huang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Ca2+ has been recognized as a key molecule for chondrocytes, however, the role and mechanism of spontaneous [Ca 2+] i signaling in cartilaginous extracellular matrix (ECM) metabolism regulation are unclear. Here we found that spontaneous Ca 2+ signal of in‐situ porcine chondrocytes was [Ca 2+] o dependent, and mediated by [Ca 2+] i store release. T‐type voltage‐dependent calcium channel (T‐VDCC) mediated [Ca 2+] o influx was associated with decreased cell viability and expression levels of ECM deposition genes. Further analysis revealed that chondrocytes expressed both inositol 1,4,5‐trisphosphate receptor (InsP3R) and Orai isoforms. Inhibition of endoplasmic reticulum (ER) Ca 2+ release and store‐operated calcium entry significantly abolished spontaneous [Ca 2+] i signaling of in‐situ chondrocytes. Moreover, blocking ER Ca 2+ release with InsP3R inhibitors significantly upregulated ECM degradation enzymes production, and was accompanied by decreased proteoglycan and collagen type II intensity. Taken together, our data provided evidence that spontaneous [Ca 2+] i signaling of in‐situ porcine chondrocytes was tightly regulated by [Ca 2+] o influx, InsP3Rs mediated [Ca 2+] i store release, and Orais mediated calcium release‐activated calcium channels activation. Both T‐VDCC mediated [Ca 2+] o influx and InsP3Rs mediated ER Ca 2+ release were found crucial to cartilaginous ECM metabolism through distinct regulatory mechanisms.

show abstract

Transcriptome‐based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late‐stage osteoarthritic cartilage

Matta

Lewis

Fellows

et al. 2021

Journal Cellular Physiology

View full text Add to dashboard Cite

Chondrogenic progenitor cells (CPCs) may be used as an alternative source of cells with potentially superior chondrogenic potential compared to mesenchymal stem cells (MSCs), and could be exploited for future regenerative therapies targeting articular cartilage in degenerative diseases such as osteoarthritis (OA). In this study,This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

Orai1–Orai2 complex is involved in store-operated calcium entry in chondrocyte cell lines

Cited by 41 publications

References 52 publications

Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment

Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment

Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism

Transcriptome‐based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late‐stage osteoarthritic cartilage

Contact Info

Product

Resources

About