Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism.
J Cell Physiol
; 234(6): 9711-9722, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30370672
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cartilagem
/
Sinalização do Cálcio
/
Matriz Extracelular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article