Intracellular calcium oscillations in articular chondrocytes induced by basic calcium phosphate crystals lead to cartilage degradation

Nguyen, Christelle; Lieberherr, Michèle; Bréchot, Christian; Velard, Frédéric; Côme, D.; Lioté, Frédéric; Ea, Hang‐Korng

doi:10.1016/j.joca.2012.07.017

Cited by 29 publications

(15 citation statements)

References 38 publications

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“…Several experimental data supported that intracellular Ca(2+) variations could mediate catabolic responses in OA chondrocytes [16,17]. In the adjuvant-induced arthritis rat model, treatment with amiloride, a voltage-gated Ca(2+) channel blocker, significantly decreased Mankin scores, while increased Col II and AGG mRNA and protein expression and reduced articular cartilage destruction [16].…”

Section: Discussionmentioning

confidence: 99%

“…In the adjuvant-induced arthritis rat model, treatment with amiloride, a voltage-gated Ca(2+) channel blocker, significantly decreased Mankin scores, while increased Col II and AGG mRNA and protein expression and reduced articular cartilage destruction [16]. More recently, it has been shown that intracellular calcium oscillations in articular chondrocytes induced by basic calcium phosphate crystals led to cartilage degradation [17]. This can be combined with our data that the PLC-γ1/IP3/Ca(2+)/CaMK II axis is more dominant than the PLC-γ1/DAG/PKC axis in PLC-γ1-dependent ECM synthesis of human OA chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

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Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Zeng

Cui

Liu

et al. 2014

IJMS

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Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation including extracellular matrix (ECM) degradation and cell loss. It is known that phosphoinositide-specific phospholipase γ1 (PLCγ1) can trigger several signaling pathways to regulate cell metabolism. However, whether this kinase is expressive and active in human OA chondrocytes and its role in the pathological progression of OA have not been investigated. The current study was designed to investigate the PLCγ1 expression in human OA cartilage, and whether PLCγ1 was involved in the ECM synthesis had been further explored using cultured human OA chondrocytes. Our results indicated that PLCγ1 was highly expressed in human OA chondrocytes. In our further study using the cultured human OA chondrocytes, the results demonstrated that the disruption of PLCγ1 by its inhibitor, U73122, and siRNA contributed to the ECM synthesis of human OA chondrocytes through regulating the expression of ECM-related signaling molecules, including MMP-13, Col II, TIMP1, Sox-9, and AGG. Furthermore, PLCγ1/IP3/Ca(2+)/CaMK II signaling axis regulated the ECM synthesis of human chondrocytes through triggering mTOR/P70S6K/S6 pathway. In summary, our results suggested that PLC-γ1 activities played an important role in the ECM synthesis of human OA chondrocytes, and may serve as a therapeutic target for treating OA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Zeng

Cui

Liu

et al. 2014

IJMS

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“…Ca 2+ oscillations have been reported in a great variety of non-excitable cells including pancreatic β-cells [49], embryonic stem cells (ESCs) [47], chondroblasts [11,35], chondrocytes [40] and human MSCs [22,24]. This is the first study to report that human chondroprogenitor cells derived from regions with minor lesions of osteoarthritic articular cartilage (CPCs) are also characterised by a similarly dynamic Ca 2+ homeostasis.…”

Section: Dynamics Of Cytosolic [Ca 2+ ]Imentioning

confidence: 96%

“…Indeed, NMDA-receptors with altered subunit composition and activity were described in OA chondrocytes [44]; furthermore, intracellular calcium oscillations associated with inorganic calcium crystal-induced cartilage matrix degradation were also observed [40]. These alterations can serve as a background for modified metabolism and altered physiological properties of these cells.…”

Section: Introductionmentioning

confidence: 99%

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Matta

Fodor

Miosge

et al. 2014

Pflugers Arch - Eur J Physiol

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Osteoarthritis (OA) is the most common form of chronic musculoskeletal disorders. A migratory stem cell population termed chondrogenic progenitor cells (CPC) with in vitro chondrogenic potential was previously isolated from OA cartilage. Since intracellular Ca 2+ signalling is an important regulator of chondrogenesis, we aimed to provide a detailed understanding of the Ca 2+ homeostasis of CPCs. In this work, CPCs immortalised by lentiviral administration of the human telomerase reverse transcriptase (hTERT) and grown in monolayer cultures were studied. Expressions of all three IP3Rs were confirmed, but no RyR subtypes were detected. Ca 2+ oscillations observed in CPCs were predominantly dependent on Ca 2+ release and store replenishment via store-operated Ca 2+ entry; CPCs express both STIM1 and Orai1 proteins. Expressions of adenosine receptor mRNAs were verified, and adenosine elicited Ca 2+ transients. Various P2 receptor subtypes were identified; P2Y1 can bind ADP; P2Y4 is targeted by UTP; and ATP may evoke Ca 2+ transients via detected P2X subtypes, as well as P2Y1 and P2Y2. Enzymatic breakdown of extracellular nucleotides by apyrase completely abrogated Ca 2+ oscillations, suggesting that an autocrine/paracrine purinergic mechanism may drive Ca 2+ oscillations in these cells.As CPCs possess a broad spectrum of functional molecular elements of Ca 2+ signalling, Ca 2+ -dependent regulatory mechanisms can be supposed to influence their differentiation potential.

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“…Interestingly, bovine articular chondrocytes within cartilage explants, when exposed to basic calcium phosphate crystals, had significant increases in intracellular calcium content, which is correlated with cartilage matrix degradation [80]. Another ECM component that affects chondrocyte metabolism is fibronectin, which showed a significant positive correlation between chondrocyte apoptosis and fibronectin content [81].…”

Section: The Effects Of Changes In Extracellular Matrix On Articulmentioning

confidence: 99%

The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

Maldonado

Nam

2013

BioMed Research International

385

297

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Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.

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Intracellular calcium oscillations in articular chondrocytes induced by basic calcium phosphate crystals lead to cartilage degradation

Abstract: BCP crystals can induce variation in iCa(2+) content and oscillations in articular chondrocytes. Furthermore, BCP crystal-induced changes in iCa(2+) content play a pivotal role in BCP catabolic effects on articular cartilage.

Cited by 29 publications

References 38 publications

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

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