Τίτλος:
The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020 The Author(s).
Συγγραφείς:
Nasi, S.
Ehirchiou, D.
Chatzianastasiou, A.
Nagahara, N.
Papapetropoulos, A.
Bertrand, J.
Cirino, G.
So, A.
Busso, N.
Περιοδικό:
Arthritis Research and Therapy
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
3 mercaptopyruvate sulfurtransferase; hydrogen sulfide; hydroxyapatite; interleukin 6; 3-mercaptopyruvate sulphurtransferase; hydrogen sulfide; interleukin 6; protective agent; sulfurtransferase, adult; aged; animal cell; animal experiment; animal model; animal tissue; Article; bone mineralization; calcification; cartilage degeneration; chondrocyte; clinical article; controlled study; cytokine release; disease course; disease exacerbation; disease severity; down regulation; enzyme analysis; experimental osteoarthritis; female; human; human tissue; in vitro study; in vivo study; knee meniscus; meniscectomy; middle aged; mouse; nonhuman; oxidative stress; protein expression; signal transduction; animal; articular cartilage; C57BL mouse; calcinosis; diagnostic imaging; genetics; knee osteoarthritis; knockout mouse; metabolism; micro-computed tomography; pathology; procedures; very elderly, Aged; Aged, 80 and over; Animals; Calcinosis; Cartilage, Articular; Chondrocytes; Female; Humans; Hydrogen Sulfide; Interleukin-6; Meniscectomy; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Osteoarthritis, Knee; Protective Agents; Sulfurtransferases; X-Ray Microtomography
DOI:
10.1186/s13075-020-02147-6
