Abstract:
BACKGROUND:Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H2S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development. METHODS:3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST-/- meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST-/- cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated. RESULTS:3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST-/- mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes. CONCLUSION:3-MST-generated H2S protects against joint calcification and experimental OA. Enhancing H2S production in chondrocytes may represent a potential disease modifier to treat OA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Nasi S,Ehirchiou D,Chatzianastasiou A,Nagahara N,Papapetropoulos A,Bertrand J,Cirino G,So A,Busso Ndoi
10.1186/s13075-020-02147-6subject
Has Abstractpub_date
2020-03-17 00:00:00pages
49issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-020-02147-6journal_volume
22pub_type
杂志文章abstract:INTRODUCTION:Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2833
更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1010
更新日期:2003-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4213
更新日期:2013-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4237
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1208-6
更新日期:2017-01-13 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3122
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar782
更新日期:2003-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3098
更新日期:2010-01-01 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2015-08-12 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1117-8
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1820-3
更新日期:2019-01-29 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 评论,杂志文章,评审
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2016-10-25 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2013-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2016-06-13 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3778
更新日期:2012-03-14 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-03-23 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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更新日期:2012-09-28 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 评论,社论
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更新日期:2010-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2020-10-15 00:00:00
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pub_type: 杂志文章
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更新日期:2006-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 评论,社论
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