Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity

Sadowska, Aleksandra; Kameda, Takuya; Krupková, Olga; Wuertz-Kozak,

doi:10.22203/ecm.v036a17

Cited by 27 publications

(24 citation statements)

References 169 publications

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“…Changes to the extracellular ionic composition and osmolarity have profound effects on ECM metabolism by connective tissue cells. This has been demonstrated in articular cartilage and intervertebral disc explants, isolated chondrocytes, and chondrocytes cultured in alginate [ 45 , 67 – 69 ], as well as isolated intervertebral disc cells [ 70 ]. In articular cartilage, variations in medium osmolarity above or below that in native non-degenerate cartilage, inhibit optimal matrix GAG and protein synthesis [ 45 ].…”

Section: Cartilage Osmolarity Swelling In Early Oa and Chondrocyte mentioning

confidence: 98%

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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Section: Cartilage Osmolarity Swelling In Early Oa and Chondrocyte mentioning

confidence: 98%

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

2019

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“…Among the ASIC isotypes, ASIC1a had been attracted much attention because of its ability to mediate the Ca 2+ influx ([Ca 2+ ]i) and endoplasmic reticulum (ER) stress, which would activate the apoptosis process. With Psalmotoxin (PcTx1), the specific inhibitor of ASIC1a, the increase of [Ca 2+ ] i and necrosis in NPC induced by acid were blocked [16,17] (Table 3).…”

Section: Np Degenerationmentioning

confidence: 99%

Acid-sensing ion channels mediate the degeneration of intervertebral disc via various pathways—A systematic review

et al. 2019

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To elucidate the pathological significance of acid-sensing ion channels (ASICs) in intervertebral disc degeneration (IVDD), the database of Medline, Web of Science, and EmBase were carefully screened. Search terms used in each database varied slightly to optimize results. Data relating to the correlation between ASICs and IVDD was systematically collected and integrated into the review. 11 basic science studies, containing the related information, were finally identified for inclusion. Intervertebral disc degeneration (IVDD) is a common disease in middle-aged and elderly people, which has a great impact on patients’ quality of life. Many research teams have attempted to elucidate the pathogenesis of this degenerative disease, and have made considerable progress. Acid-sensing ion channels (ASICs) were once reported to be able to regulate the apoptosis process of chondrocytes in joint cartilage, which has been transplanted into the IVDD-related research. ASIC1a functions as the mediator for cells in nucleus pulposus (NP) and endplate (EP), with whose activation the apoptosis process would be accelerated. Moreover, ASIC1a’s activation could also regulate the anabolism in chondrocytes of EP, facilitating the degeneration. ASIC3 would only promote the degeneration in NP, possibly via its pro-inflammatory effect. The distribution of ASICs in NP, EP, annulus fibrosus, and the particular functions of ASIC1a and ASIC3 remind us about the pathological significance of ASICs in IVDD, which could be a promising therapeutic target in future treatment for IVDD.

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“…Moreover, in contrary to bovine tails, human spine experiences day-to-day mechanical loading from body weight and daily activities, which not only can act as a stimuli for IVD cells and TRP channels, but also lead to daily osmotic shifts (e.g. increased osmotic pressure during daily life activities and reduced osmotic pressure during rest periods) (Schmidt et al, 2010;Chan et al, 2011;Sadowska et al, 2018). Hence, dynamic mechanical loading as well as diurnal osmotic loading could be incorporated in the future studies.…”

Section: A B C D Ementioning

confidence: 99%

Hypo-Osmotic Loading Induces Expression of IL-6 in Nucleus Pulposus Cells of the Intervertebral Disc Independent of TRPV4 and TRPM7

et al. 2020

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Painful intervertebral disc (IVD) degeneration is an age-related process characterized by reduced tissue osmolarity, increased catabolism of the extracellular matrix, and elevated levels of pro-inflammatory molecules. With the aging population and constantly rising treatment costs, it is of utmost importance to identify potential therapeutic targets and new pharmacological treatment strategies for low back pain. Transient receptor potential (TRP) channels are a family of Ca 2+ permeable cell membrane receptors, which can be activated by multitude of stimuli and have recently emerged as contributors to joint disease, but were not investigated closer in the IVD. Based on the gene array screening, TRPC1, TRPM7, and TRPV4 were overall the most highly expressed TRP channels in bovine IVD cells. We demonstrated that TRPV4 gene expression was down-regulated in hypo-osmotic condition, whereas its Ca 2+ flux increased. No significant differences in Ca 2+ flux and gene expression were observed for TRPM7 between hypo-and iso-osmotic groups. Upon hypo-osmotic stimulation, we overall identified via RNA sequencing over 3,000 up-or down-regulated targets, from which we selected aggrecan, ADAMTS9, and IL-6 and investigated whether their altered gene expression is mediated through either the TRPV4 or TRPM7 channel, using specific activators and inhibitors (GSK1016790A/ GSK2193874 for TRPV4 and Naltriben/NS8593 for TRPM7). GSK1016790A induced the expression of IL-6 under iso-osmotic condition, alike to hypo-osmotic stimulation alone, indicating that this effect might be TRPV4-mediated. However, using the TRPV4 blocker GSK2193874 failed to prevent the increase of IL-6 under hypo-osmotic condition. A treatment with TRPM7-activator did not cause significant changes in the gene expression of tested targets. In conclusion, while TRPV4 and TRPM7 are likely involved

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Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity

Cited by 27 publications

References 169 publications

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

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

Acid-sensing ion channels mediate the degeneration of intervertebral disc via various pathways—A systematic review

Hypo-Osmotic Loading Induces Expression of IL-6 in Nucleus Pulposus Cells of the Intervertebral Disc Independent of TRPV4 and TRPM7

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