Altered spontaneous calcium signaling of in situ chondrocytes in human osteoarthritic cartilage

Gong, Xiaoyuan; Xie, Wensheng; Wang, Bin; Gu, Lingchuan; Wang, Fuyou; Ren, Xiang; Chen, Cheng; Yang, Liu

doi:10.1038/s41598-017-17172-w

Cited by 23 publications

(16 citation statements)

References 44 publications

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“…Because chondrocytes located in statically cultured cartilage explants are not compressed or exposed to osmotic tension, VDCCs might be the major candidate responsible for [Ca 2+ deposition (Fodor et al, 2013;Xu et al, 2009). This was supported by our previous study, in which we showed that chondrocytes in early degenerated human articular cartilage displayed stronger spontaneous [Ca 2+ ] i signaling, and correspondingly increased protein abundance of Ca v 3.3 (the α1 subunit of T-VDCC; Gong et al, 2017).…”

Section: Discussionsupporting

confidence: 83%

“…Recent studies discovered that both isolated and in‐situ animal chondrocytes are able to display repetitive [Ca 2+ ] i signaling without any extracellular stimuli (O'Conor et al, ; Zhou, David et al, ). In addition, our recent study showed that in‐situ chondrocytes located in healthy human articular cartilage tissue were also capable to produce the zonal and OA severity dependent spontaneous [Ca 2+ ] i signaling (Gong et al, ). Given the fact that correlation between spontaneous [Ca 2+ ] i signaling and cartilaginous ECM maintenance has been demonstrated (Zhou, Park et al, ), spontaneous [Ca 2+ ] i signaling might be a key indicator of OA progression.…”

Section: Discussionmentioning

confidence: 99%

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

Gong

Huang

et al. 2018

Journal Cellular Physiology

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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.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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

Gong

Huang

et al. 2018

Journal Cellular Physiology

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“…Articular cartilage and subchondral bone make an osteochondral unit in the joints [ 15 ]. Articular cartilage, including the superficial, middle, and deep layers [ 16 ], is responsible for biomechanical properties of a joint such as distribution of force, absorption of shock, and load-bearing that enables a pain-free and frictionless movement of the joint [ 17 , 18 , 19 ]. The superficial layer with a parallel structure of collagens and a high density of chondrocytes protects against shear and tensile stresses [ 16 , 20 ].…”

Section: Osteochondral Tissuementioning

confidence: 99%

Bioactive Inks Development for Osteochondral Tissue Engineering: A Mini-Review

Bakhtiary

Liu

Ghorbani

2021

Gels

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Nowadays, a prevalent joint disease affecting both cartilage and subchondral bone is osteoarthritis. Osteochondral tissue, a complex tissue unit, exhibited limited self-renewal potential. Furthermore, its gradient properties, including mechanical property, bio-compositions, and cellular behaviors, present a challenge in repairing and regenerating damaged osteochondral tissues. Here, tissue engineering and translational medicine development using bioprinting technology provided a promising strategy for osteochondral tissue repair. In this regard, personalized stratified scaffolds, which play an influential role in osteochondral regeneration, can provide potential treatment options in early-stage osteoarthritis to delay or avoid the use of joint replacements. Accordingly, bioactive scaffolds with possible integration with surrounding tissue and controlling inflammatory responses have promising future tissue engineering perspectives. This minireview focuses on introducing biologically active inks for bioprinting the hierarchical scaffolds, containing growth factors and bioactive materials for 3D printing of regenerative osteochondral substitutes.

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“…It is assumed to involve in cell sensing substrate stiffness by locally altering the Ca 2+ permeability [28,29]. Since calcium signaling plays an important role in multiple signaling pathways and mechanotransduction in chondrocytes [30,31], substrate stiffness may modulate the chondrocyte mechanotransduction via the TRPV4-mediated Ca 2+ signaling, which eventually affects cell function [15]. Collectively, these ndings highlight the potential role of substrate stiffness in regulating the RVD response and TRPV4-mediated calcium signaling in chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Substrate Stiffness-Dependent Regulatory Volume Decrease and Calcium Signaling in Chondrocytes

Zhang¹,

Zhang²,

Wu³

et al. 2020

Preprint

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The pericellular matrix stiffness is strongly associated with its biochemical and structural changes During the aging and osteoarthritis progresses of articular cartilage. However, how substrate stiffness modulates the chondrocyte regulatory volume decrease (RVD) and calcium signaling remains unknown. This study aims to investigate the effects of substrate stiffness on the chondrocyte RVD and calcium signaling by recapitulating the physiologically relevant substrate stiffness. Our results showed that substrate stiffness induced completely different dynamical deformation between the cell swelling and recovering progresses. Chondrocytes swelled faster on the soft substrate but recovered slower than the stiff substrate during the RVD response induced by the hypo-osmotic challenge. We found that stiff substrate enhanced the cytosolic Ca2+ oscillation of chondrocytes in the iso-osmotic medium. More importantly, chondrocytes exhibited a distinctive cytosolic Ca2+ oscillation during the RVD response. Soft substrate significantly improved the Ca2+ oscillation during the cell swelling whereas stiff substrate enhanced the cytosolic Ca2+ oscillation during the cell recovering. Our work also suggests that TRPV4 channel are involved in the chondrocyte sensing substrate stiffness and RVD response by mediating Ca2+ signaling in a stiffness-dependent manner. It helps to understand a previously unidentified relationship between substrate stiffness and RVD response under the hypo-osmotic challenge.

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Altered spontaneous calcium signaling of in situ chondrocytes in human osteoarthritic cartilage

Cited by 23 publications

References 44 publications

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

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

Bioactive Inks Development for Osteochondral Tissue Engineering: A Mini-Review

Substrate Stiffness-Dependent Regulatory Volume Decrease and Calcium Signaling in Chondrocytes

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