Involvement of Transient Receptor Potential Vanilloid Channel 2 in the Induction of Lubricin and Suppression of Ectopic Endochondral Ossification in Mouse Articular Cartilage
© 2021, American College of Rheumatology..
OBJECTIVE: Transient receptor potential vanilloid channel 2 (TRPV2) is a Ca2+ -permeable channel and plays a role in mediating intracellular Ca2+ current via mechanical stimuli. This study was undertaken to examine the expression and role of TRPV2 in adult articular cartilage and the development of osteoarthritis (OA).
METHODS: We examined TRPV2 expression in mouse and human articular cartilage. We analyzed the development of OA in Col2a1-CreERt2 ;Trpv2fl/fl mice and Trpv2fl/fl littermates in the resection of the medial meniscus and medial collateral ligament model (n = 5 each), the destabilization of the medial meniscus model (n = 5 each), and the aging mouse model (n = 8-9 each). We examined marker protein expression in these joints, Ca2+ influx by mechanical stimuli, and downstream pathways in vitro.
RESULTS: TRPV2 was expressed in mouse and human articular cartilage and ectopic ossification lesions. In all mouse models of OA examined, Col2a1-CreERt2 ;Trpv2fl/fl mice were observed to have enhanced degradation of articular cartilage accompanied by decreased expression of lubricin/Prg4, and marked formation of periarticular ectopic ossification. Mechanical stress-induced Ca2+ influx was decreased by Trpv2 knockout (KO). Prg4 induction by fluid-flow shear stress was diminished in Trpv2-KO mouse chondrocytes, and this was mediated by the Ca2+ /calmodulin-dependent protein kinase kinase-cyclic AMP response element binding protein axis. Hypertrophic differentiation was enhanced in Trpv2-KO mouse chondrocytes. Increased activity of calcineurin and nuclear translocation of nuclear factor in activated T cells 1 induced by fluid-flow shear stress or TRP agonist treatment was reversed by Trpv2 knockout.
CONCLUSION: Our findings demonstrate regulation of articular cartilage by TRPV2 through Prg4 induction and suppression of ectopic ossification.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Arthritis & rheumatology (Hoboken, N.J.) - 73(2021), 8 vom: 16. Aug., Seite 1441-1450 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nakamoto, Hideki [VerfasserIn] |
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| Links: |
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| Themen: |
Glycoproteins |
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| Anmerkungen: |
Date Completed 08.09.2021 Date Revised 08.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/art.41684 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321458796 |
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| 100 | 1 | |a Nakamoto, Hideki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Involvement of Transient Receptor Potential Vanilloid Channel 2 in the Induction of Lubricin and Suppression of Ectopic Endochondral Ossification in Mouse Articular Cartilage |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 08.09.2021 | ||
| 500 | |a Date Revised 08.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021, American College of Rheumatology. | ||
| 520 | |a OBJECTIVE: Transient receptor potential vanilloid channel 2 (TRPV2) is a Ca2+ -permeable channel and plays a role in mediating intracellular Ca2+ current via mechanical stimuli. This study was undertaken to examine the expression and role of TRPV2 in adult articular cartilage and the development of osteoarthritis (OA) | ||
| 520 | |a METHODS: We examined TRPV2 expression in mouse and human articular cartilage. We analyzed the development of OA in Col2a1-CreERt2 ;Trpv2fl/fl mice and Trpv2fl/fl littermates in the resection of the medial meniscus and medial collateral ligament model (n = 5 each), the destabilization of the medial meniscus model (n = 5 each), and the aging mouse model (n = 8-9 each). We examined marker protein expression in these joints, Ca2+ influx by mechanical stimuli, and downstream pathways in vitro | ||
| 520 | |a RESULTS: TRPV2 was expressed in mouse and human articular cartilage and ectopic ossification lesions. In all mouse models of OA examined, Col2a1-CreERt2 ;Trpv2fl/fl mice were observed to have enhanced degradation of articular cartilage accompanied by decreased expression of lubricin/Prg4, and marked formation of periarticular ectopic ossification. Mechanical stress-induced Ca2+ influx was decreased by Trpv2 knockout (KO). Prg4 induction by fluid-flow shear stress was diminished in Trpv2-KO mouse chondrocytes, and this was mediated by the Ca2+ /calmodulin-dependent protein kinase kinase-cyclic AMP response element binding protein axis. Hypertrophic differentiation was enhanced in Trpv2-KO mouse chondrocytes. Increased activity of calcineurin and nuclear translocation of nuclear factor in activated T cells 1 induced by fluid-flow shear stress or TRP agonist treatment was reversed by Trpv2 knockout | ||
| 520 | |a CONCLUSION: Our findings demonstrate regulation of articular cartilage by TRPV2 through Prg4 induction and suppression of ectopic ossification | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Prg4 protein, mouse |2 NLM | |
| 650 | 7 | |a Proteoglycans |2 NLM | |
| 650 | 7 | |a TRPV Cation Channels |2 NLM | |
| 650 | 7 | |a Transient Receptor Potential Channels |2 NLM | |
| 650 | 7 | |a lubricin |2 NLM | |
| 700 | 1 | |a Katanosaka, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Chijimatsu, Ryota |e verfasserin |4 aut | |
| 700 | 1 | |a Mori, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Xuan, Fengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Yano, Fumiko |e verfasserin |4 aut | |
| 700 | 1 | |a Omata, Yasunori |e verfasserin |4 aut | |
| 700 | 1 | |a Maenohara, Yuji |e verfasserin |4 aut | |
| 700 | 1 | |a Murahashi, Yasutaka |e verfasserin |4 aut | |
| 700 | 1 | |a Kawaguchi, Kohei |e verfasserin |4 aut | |
| 700 | 1 | |a Yamagami, Ryota |e verfasserin |4 aut | |
| 700 | 1 | |a Inui, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Taketomi, Shuji |e verfasserin |4 aut | |
| 700 | 1 | |a Taniguchi, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kanagawa, Motoi |e verfasserin |4 aut | |
| 700 | 1 | |a Naruse, Keiji |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Sakae |e verfasserin |4 aut | |
| 700 | 1 | |a Saito, Taku |e verfasserin |4 aut | |
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