Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis

Karlsson, Camilla; Dehne, Tilo; Lindahl, Anders; Brittberg, Mats; Pruß, Axel; Sittinger, Michael; Ringe, Jochen

doi:10.1016/j.joca.2009.12.002

Cited by 233 publications

(277 citation statements)

References 35 publications

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“…Firstly, healthy and OA chondrocytes have an altered complement of plasma membrane ion channels and porins, which can at least partially be attributed to ECM degradation during OA. In particular, a set of ion channels including Ca 2+ activated potassium channels (BK and IK), Ca 2+ activated Cl -channels, aquaporin-1 (AQP1), as well as voltage-gated K + channels or the piezo-type mechanosensitive ion channel 2 (Piezo2) were differentially expressed in healthy vs. OA cartilage [59][60][61]. Most of these channels play important roles in setting the RMP.…”

Section: Discussionmentioning

confidence: 99%

Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease

2015

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Chondrocytes, the single cell type in adult articular cartilage, have conventionally been considered to be non-excitable cells. However, recent evidence suggests that their resting membrane potential (RMP) is less negative than that of excitable cells, and they are fully equipped with channels that control ion, water, and osmolyte movement across the chondrocyte membrane. Among calcium-specific ion channels, members of the voltage-dependent calcium channel (VDCC) family are expressed in chondrocytes where they are functionally active. Ltype VDCC inhibitors such as nifedipine and verapamil have contributed to our understanding of the roles of these ion channels in chondrogenesis, chondrocyte signalling, and mechanotransduction. In this narrative review, we discuss published data indicating that VDCC function is vital for chondrocyte health, especially in regulating proliferation and maturation.We also highlight the fact that activation of VDCC function appears to accompany various inflammatory aspects of osteoarthritis (OA) and, based on in vitro data, the application of nifedipine and/or verapamil may be a promising approach for ameliorating OA severity.However, very few studies on clinical outcomes are available regarding the influence of calcium antagonists, which are used primarily for treating cardiovascular conditions in OA patients. This review is intended to stimulate further research on the chondrocyte 'channelome', contribute to the development of novel therapeutic strategies, and facilitate the retargeting and repositioning of existing pharmacological agents currently used for other comorbidities for the treatment of OA.

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Section: Discussionmentioning

confidence: 99%

Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease

2015

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“…These changes also showed major overlap with previous microarray comparisons of expression in OA and non-OA cartilage. [13][14][15] …”

Section: Genome-wide Expression Analysis Of Intact Oa Cartilagementioning

confidence: 99%

Stratification of knee osteoarthritis: two major patient subgroups identified by genome wide expression analysis of articular cartilage

Soul

Dunn

Anand

et al. 2018

Osteoarthritis and Cartilage

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“…Since arthritic cartilage matrix undergoes profound changes especially at the late stages of the disease, it is logical to assume that cells in OA-affected cartilage may be characterised by a unique assembly of plasma membrane ion channels and transporters that regulate their function and phenotype, and consequently maintain communication with the extracellular space. Indeed, according to a genome-wide analysis that compared the mRNA transcriptome of chondrocytes isolated from articular cartilage of healthy and OA patients, the expression of several plasma membrane ion channels with a putative role in volume regulation, apoptosis, and proliferation was found to be significantly altered [20].…”

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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Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis

Cited by 233 publications

References 35 publications

Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease

Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease

Stratification of knee osteoarthritis: two major patient subgroups identified by genome wide expression analysis of articular cartilage

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

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