Abstract
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.
Highlights
Osteoarthritis (OA) is the most common articular chronic disease
MMP-13 is an enzyme constitutively expressed in the chondrocyte that degrades collagenous extracellular matrix (ECM) [15]
The examination of macroscopic parameters and joint goniometry were completed in order to evaluate the effect of the intraarticular administration of H2S on joints with surgically induced lesions
Summary
Osteoarthritis (OA) is the most common articular chronic disease. Despite this high incidence in the population, especially in the elderly, its etiology has not been completely elucidated yet. OA was classically considered to be mainly a consequence of the “wear and tear” of the articular cartilage, we know that it is a more complex pathology that involves both mechanical and biological processes occurring in the cartilage but in the entire joint [1] In this regard, the increased production of pro-inflammatory mediators in the cartilage and synovial tissue contribute to cartilage destruction that in turn amplifies joint inflammation, creating a vicious circle that contributes to OA development [2,3,4]. The expression of inducible isoform of cyclooxygenase, COX-2, is elicited by inflammatory stimuli and oxidative stress [5,6] This enzyme is responsible for the synthesis of PGE2, one of the most important pro-inflammatory prostaglandins in the OA [7]. Its aberrant expression and activity elicited by pro-inflammatory mediators and oxidative stress has been associated with diseases such as OA [15,16,17]
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