Session Information
Date: Monday, November 9, 2015
Title: Biology and Pathology of Bone and Joint Poster I: Osteoarthritis Pathogenesis
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Hydrogen sulfide (H2S) is, next to NO and CO, the third endogenous gasotransmitter. It has been shown that in some pathologies, such as hypertension, cardiovascular disease or diabetes type II, H2S endogenous levels or biosynthesis are significantly reduced and that exogenous administration might be helpful. Previous experiments by our group have demonstrated that H2S releasing compounds have anti-inflammatory and anti-catabolic effects on IL1β-stimulted OA chondrocytes. Therefore our hypothesis in the present work was that OA patients might also have lower endogenous H2S levels.
Methods: Joint tissues and blood samples were obtained from patients of the Orthopedic or Rheumatology Services of the University Hospital A Coruña (CHUAC), or volunteers (blood only), after written informed consent. The mRNA expression of the H2S production enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CTH) and mercaptopyruvate sulfurtransferase (MPST) was analyzed in cartilage, synovial membrane and subchondral bone. Immunohistochemistry and quantification with ImageJ was performed to evaluate the location and abundance of the CBS, CTH and MPST. Hydrogen sulfide concentration was measured using a selective ion microelectrode. Direct H2S concentration was measured in 200 μL of fresh serum after incubation with 200 μL of an antioxidant buffer (AB) for 1h. Likewise, H2S production from cartilage was measured by incubating cartilage disks in 200 μL of the same AB for 2 h.
Results: We found that all three enzymes, CBS, CTH and MPST were expressed in all tested joint tissues. CBS was slightly reduced in the OA cartilage, but no statistically significant differences were detected for this enzyme, nor CTH, in any tissue. Notably, however, MPST mRNA expression was significantly reduced in OA cartilage with respect to normal controls. Immunohistochemistry also showed decreased levels of this enzyme in cartilage. On the other hand, statistically significant differences were also found in the H2S production measured from OA with respect to non OA cartilage samples. Indeed, OA cartilage H2S production was 0.105 ± 0.042 nmoles/g of cartilage (mean ± SE, n=13) in OA tissue while that of healthy cartilage was 0.433 ± 0.110 nmoles/g of cartilage (mean ± SE, n=5), p<0.05. These differences, however, were not reflected in the H2S concentrations in blood serum samples, where no statistically significant differences were found (OA serum: 56.48 ± 7.24 μM (mean ± SE, n=38) vs. N serum: 72.18 ± 10.66 μM (mean ± SE, n=28), p>0.05).
Conclusion: Local H2S biosynthesis is reduced in the OA joint. This is the result, at the least, of a reduced mRNA expression and protein abundance of MPST. Since MPST is predominantly a mitochondrial enzyme, this deficit might be another factor that causes the mitochondrial dysfunction that is known to contribute to OA pathogenesis.
To cite this abstract in AMA style:
Vela-Anero A, Gato-Calvo L, Ruiz-Romero C, Meijide-Failde R, Blanco FJ, Burguera EF. Reduced Hydrogen Sulfide Synthesis in the Joint, a New Player in the Pathogenesis of Osteoarthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/reduced-hydrogen-sulfide-synthesis-in-the-joint-a-new-player-in-the-pathogenesis-of-osteoarthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-hydrogen-sulfide-synthesis-in-the-joint-a-new-player-in-the-pathogenesis-of-osteoarthritis/