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Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis

1
Grupo de Terapia Celular y Medicina Regenerativa, Universidad de A Coruña, Agrupación Estratégica CICA- INIBIC, Complexo Hospitalario Universitario A Coruña, Campus Oza, 15006 A Coruña, Spain
2
Grupo de Investigación en Reumatología (GIR), INIBIC-Complexo Hospitalario Universitario A Coruña, Sergas, As Xubias, 15006 A Coruña, Spain
3
Centro de investigación biomédica en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
4
Grupo de Envejecimiento e Inflamación, Agrupación Estratégica CICA- INIBIC, Complexo Hospitalario Universitario A Coruña, Sergas, Universidad de A Coruña, As Xubias, 15006 A Coruña, Spain
5
Grupo de Investigación de Reumatología y Salud (GIR), Departamento de Fisioterapia, Medicina y Ciencias Biomédicas, Facultad de Fisioterapia, Agrupación Estrategica CICA-INIBIC, Universidade da Coruña, Campus de Oza, 15006 A Coruña, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(19), 7421; https://doi.org/10.3390/ijms21197421
Received: 14 September 2020 / Revised: 1 October 2020 / Accepted: 6 October 2020 / Published: 8 October 2020
(This article belongs to the Special Issue Redox Signaling and Oxidative Stress in Bone Health and Disease)
Osteoarthritis (OA) is the most common articular chronic disease. However, its current treatment is limited and mostly symptomatic. Hydrogen sulfide (H2S) is an endogenous gas with recognized physiological activities. The purpose here was to evaluate the effects of the intraarticular administration of a slow-releasing H2S compound (GYY-4137) on an OA experimental model. OA was induced in Wistar rats by the transection of medial collateral ligament and the removal of the medial meniscus of the left joint. The animals were randomized into three groups: non-treated and intraarticularly injected with saline or GYY-4137. Joint destabilization induced articular thickening (≈5% increment), the loss of joint mobility and flexion (≈12-degree angle), and increased levels of pain (≈1.5 points on a scale of 0 to 3). Animals treated with GYY-4137 presented improved motor function of the joint, as well as lower pain levels (≈75% recovery). We also observed that cartilage deterioration was attenuated in the GYY-4137 group (≈30% compared with the saline group). Likewise, these animals showed a reduced presence of pro-inflammatory mediators (cyclooxygenase-2, inducible nitric oxide synthase, and metalloproteinase-13) and lower oxidative damage in the cartilage. The increment of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) levels and Nrf-2-regulated gene expression (≈30%) in the GYY-4137 group seem to be underlying its chondroprotective effects. Our results suggest the beneficial impact of the intraarticular administration of H2S on experimental OA, showing a reduced cartilage destruction and oxidative damage, and supporting the use of slow H2S-producing molecules as a complementary treatment in OA. View Full-Text
Keywords: hydrogen sulfide; osteoarthritis; oxidative damage; inflammation; Nrf-2 hydrogen sulfide; osteoarthritis; oxidative damage; inflammation; Nrf-2
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MDPI and ACS Style

Vaamonde-García, C.; Burguera, E.F.; Vela-Anero, Á.; Hermida-Gómez, T.; Filgueira-Fernández, P.; Fernández-Rodríguez, J.A.; Meijide-Faílde, R.; Blanco, F.J. Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis. Int. J. Mol. Sci. 2020, 21, 7421.

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