Regulation of chondrocyte functions by transient receptor potential cation channel V6 in osteoarthritis

Song, Tengfei; Ma, Jiguang; Guo, Lei; Yang, Peng; Zhou, Xuhui; Ye, Tianwen

doi:10.1002/jcp.25770

Cited by 21 publications

(14 citation statements)

References 37 publications

(40 reference statements)

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“…TRPV4 is a positive regulator of SOX9 and mutations in this gene are linked to chondrodysplasia [29]. In addition, TRPV6-knockout mice exhibit severe OA changes suggesting that TRPV6 may be a chondroprotective factor [30]. Accumulating evidence indicates that altered expression or function of Ca 2+ channels, including TRP channels, might be implicated in OA development [24].…”

Section: Discussionmentioning

confidence: 99%

Neuromedin B Promotes Chondrocyte Differentiation of Mesenchymal Stromal Cells via Calcineurin and Calcium Signaling

Maumus

Fonteneau

Ruiz

et al. 2020

Preprint

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Background: Articular cartilage is a complex tissue with poor healing capacities. Current approaches for cartilage repair based on mesenchymal stromal cells (MSCs) are often disappointing because of the lack of relevant differentiation factors that could drive MSC differentiation towards a stable mature chondrocyte phenotype. Methods: We used a large-scale transcriptomic approach to identify genes that are modulated at early stages of chondrogenic differentiation using the reference cartilage micropellet model. Results: We identified several modulated genes and selected neuromedin B (NMB) as one of the early and transiently modulated genes. We found that the timely regulated increase of NMB was specific for chondrogenesis and not observed during osteogenesis or adipogenesis. Furthermore, NMB expression levels correlated with the differentiation capacity of MSCs and its inhibition resulted in impaired chondrogenic differentiation indicating that NMB is required for chondrogenesis. We further showed that NMB activated the calcineurin activity through a Ca++-dependent signaling pathway. Conclusion: NMB is a newly described chondroinductive bioactive factor that upregulates the key chondrogenic transcription factor Sox9 through the modulation of Ca2+ signaling pathway and calcineurin activity.

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Section: Discussionmentioning

confidence: 99%

Neuromedin B Promotes Chondrocyte Differentiation of Mesenchymal Stromal Cells via Calcineurin and Calcium Signaling

Maumus

Fonteneau

Ruiz

et al. 2020

Preprint

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“…Full-thickness specimens were processed for immunohistochemical analysis, as previously described. 4 Briefly, after the slides were incubated with a blocking serum (Vectastain ABC Kit; Vector Laboratories, Inc., Burlingame, CA, USA) for 60 min, they were blotted and then overlaid with the primary antibody against 15-LO-1 for 2 h at room temperature. Subsequently, biotinylated secondary antibodies were added into the sections, followed by a peroxidase-labeled streptavidin–biotin staining technique (DAB Kit, Invitrogen, Paisley, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Chondrocytes were isolated from articular cartilage in the knee joints of rats as previously reported. 4 Articular cartilage tissues were cut into small pieces (<1 mm 3 ) and digested with 0.25% trypsin for 30 min, followed by digestion with 0.2% type II collagenase for 4 h. The released cells were cultured in DMEM/F12 media supplemented with 10% fetal bovine serum (FBS) and antibiotics. Once reached to 80% confluence, the cells were subjected to cyclic tensile strain with a 0.5 Hz sinusoidal curve at 5–20% elongation for 12–48 h using an Flexcell1 FX-5000 Tension System as described in the manufacturer’s manual (Flexcell International Corporation, Burlington, NC, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA from chondrocytes was extracted using TRIzol reagent (Invitrogen) as previously reported. 4 cDNA was synthesized using 1 μ g of RNA and a RevertAid First Strand cDNA Synthesis Kit (TaKaRa, Dalian, China). QRT-PCR was performed to amplify the cDNA using the SYBR Premix Ex Tag Kit (TaKaRa) and an ABI 7500 Sequencing Detection System (Applied Biosystems, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Articular chondrocyte, as the sole cell type in cartilage, is the sensor of articular cartilage homeostasis and has a critical role in maintaining the normal physiological structure and function of articular cartilage. 4 Chondrocytes are responsible for the synthesis, maintenance and degradation of the cartilage extracellular matrix (ECM), which protects the tissue against tensile stress and physical loading. 5 , 6 , 7 Previous studies demonstrated that articular chondrocyte homeostasis could be disrupted by multiple factors, such as abnormal mechanical loading, pro-inflammatory mediators and oxidative stress.…”

mentioning

confidence: 99%

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Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the pathogenesis of osteoarthritis

Chen

Yan

et al. 2017

Cell Death Dis

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15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The purpose of this study was to determine the potential role of 15-LO-1 in osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western blotting and quantitative real-time PCR in articular cartilage from the OA rat models and OA patients. To further investigate the effects of 15-LO-1 on chondrocyte functions, such as extracellular matrix (ECM) secretion, the release of matrix-degrading enzymes, the production of reactive oxygen species (ROS), cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid encoding 15-LO-1, respectively. The results showed that 15-LO-1 expression was obviously increased in articular cartilage from OA rats and OA patients. It was also found that many factor-related OA, such as mechanical loading, ROS, SNP and inflammatory factor, significantly promoted 15-LO-1 expression and activity in chondrocytes. Silencing 15-LO-1 was able to markedly alleviate mechanical loading-induced cartilage ECM secretion, cartilage-degrading enzyme secretion and ROS production. Overexpression of 15-LO-1 could inhibit chondrocyte proliferation and induce chondrocyte apoptosis. In addition, reduction of 15-LO-1 in vivo significantly alleviated OA. Taken together, these results indicate that 15-LO-1 has an important role in the disease progression of OA. Thus 15-LO-1 may be a good target for developing drugs in the treatment of OA.

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The Role of Chondrocyte Morphology and Volume in Controlling Phenotype—Implications for Osteoarthritis, Cartilage Repair, and Cartilage Engineering

2019

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Purpose of Review Articular chondrocytes are exclusively responsible for the turnover of the extracellular matrix (ECM) of hyaline cartilage. However, chondrocytes are phenotypically unstable and, if they de-differentiate into hypertrophic or fibroblastic forms, will produce a defective and weak matrix. Chondrocyte volume and morphology exert a strong influence over phenotype and a full appreciation of the factors controlling chondrocyte phenotype stability is central to understanding (a) the mechanisms underlying the cartilage failure in osteoarthritis (OA), (b) the rationale for hyaline cartilage repair, and (c) the strategies for improving the engineering of resilient cartilage. The focus of this review is on the factors involved in, and the importance of regulating, chondrocyte morphology and volume as key controllers of chondrocyte phenotype. Recent Findings The visualisation of fluorescently-labelled in situ chondrocytes within non-degenerate and mildly degenerate cartilage, by confocal scanning laser microscopy (CLSM) and imaging software, has identified the marked heterogeneity of chondrocyte volume and morphology. The presence of chondrocytes with cytoplasmic processes, increased volume, and clustering suggests important early changes to their phenotype. Results from experiments more closely aligned to the normal physico-chemical environment of in situ chondrocytes are emphasising the importance of understanding the factors controlling chondrocyte morphology and volume that ultimately affect phenotype. Summary An appreciation of the importance of chondrocyte volume and morphology for controlling the chondrocyte phenotype is advancing at a rapid pace and holds particular promise for developing strategies for protecting the chondrocytes against deleterious changes and thereby maintaining healthy and resilient cartilage.

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Regulation of chondrocyte functions by transient receptor potential cation channel V6 in osteoarthritis

Cited by 21 publications

References 37 publications

Neuromedin B Promotes Chondrocyte Differentiation of Mesenchymal Stromal Cells via Calcineurin and Calcium Signaling

Neuromedin B Promotes Chondrocyte Differentiation of Mesenchymal Stromal Cells via Calcineurin and Calcium Signaling

Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the pathogenesis of osteoarthritis

The Role of Chondrocyte Morphology and Volume in Controlling Phenotype—Implications for Osteoarthritis, Cartilage Repair, and Cartilage Engineering

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