1. Academic Validation
  2. Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism

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

  • J Cell Physiol. 2019 Jun;234(6):9711-9722. doi: 10.1002/jcp.27657.
Xiaoyuan Gong 1 Gaoming Li 1 Yang Huang 1 Zhenlan Fu 1 Xiongbo Song 1 Cheng Chen 1 Liu Yang 1
Affiliations

Affiliation

  • 1 Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
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.

Keywords

cartilage degeneration; cell viability; chondrocyte; extracellular matrix (ECM) metabolism; spontaneous [Ca2+] i signaling.

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