A cigarette smoke compound affects cartilage homeostasis

By Nidhi Saha, BDSReviewed by Danielle Ellis, B.Sc.Apr 28 2022

Cigarette smoke has been shown to deleteriously affect human health. For example, degenerative disc diseases are increasingly linked to cigarette smoking. Nearly 3% of the particle matter in cigarette smoke is hydroquinone (HQ). HQ exposure has been linked to increased apoptosis and oxidative stress of the immune cells. However, it is still unclear how cigarette smoke affects the health of joint tissue.

In vitro studies have shown that exposure to cigarette smoke accounts for 10% of cellular toxicity mediated by oxidative stress. Previous reports demonstrated how exposure to HQ promotes joint tissue degradation by activating the aryl hydrocarbon receptor (AhR) pathway in murine models of rheumatoid arthritis (RA). Smoking is also linked to the onset and progression of osteoarthritis (OA). OA has marked characteristics of progressive articular cartilage degradation. 

Study: Hydroquinone, a cigarette smoke compound, affects cartilage homeostasis through activation of the aryl hydrocarbon receptor pathway. Image Credit: Korionov / Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

The Study

A new study posted on bioRxiv* preprint server aimed at evaluating the effect of hydroquinone exposure on articular chondrocytes and its influence on cartilage homeostasis. For this evaluation primary articular chondrocytes were exposed to HQ either in the absence or presence of interleukin (IL)-1β pre-stimulation and assessed for – cell viability, oxidative stress, gene expression, and inflammatory parameters.

Results

The findings showed how HQ in a dose-dependent and time-dependent manner, decreased the chondrocyte viability. However, unlike previous studies, exposure to HQ did not lead to any variation in the apoptotic markers of articular chondrocytes during the analysis.

The articular chondrocytes in OA, undergo phenotypic changes which cause a progressive loss of biomechanical characteristics and degradation of the tissue. It was found that HQ exposure promotes the down-regulation of phenotypic markers and also induces the up-regulation of MMP-3 (a metalloprotease, capable of degrading various types of matrix proteins and collagens in the articular cartilage). Chondrocytes 2D cultures, when exposed to the xenobiotic––a benzene metabolite––exhibited a reduction in glycosaminoglycans (GAG) staining along with increased GAG release, which goes on to support the enhanced matrix remodeling activity by HQ. 

Oxidative stress in chondrocytes has been closely associated with increased degradation of the cartilage in severe OA. Previous studies have argued that nitrite production could contribute to tissue degeneration in the joints, and pollutants could promote the generation of nitric oxide (NO) and reactive oxygen species (ROS) in chondrocytes.

HQ has been associated with oxidative damage, and this study substantiates its pro-oxidative effect – which might contribute to the phenotypic changes in the articular chondrocytes, likely induced by the xenobiotic.

IL-1β – a pro-inflammatory trigger, stimulates catabolic changes, suppresses the anabolic pathways, and causes a decrease in matrix synthesis. In this study, IL-1β and HQ showed a synergistic effect by reducing the proteoglycan content and promoting oxidative stress. This suggests that in OA, cigarette smoke, as well as environmental pollutants, can enhance the inflammatory processes that lead to articular cartilage degradation.

AhR – a ligand-dependent transcription factor, when activated (by xenobiotics or pollutants) translocates to the nucleus. This was confirmed in the study, wherein, AhR, on HQ exposure translocated to the nucleus, formed a heterodimer with AhR nuclear translocator (ARNT), and promoted the target gene transcription.

The AhR pathway activation has mediated various detrimental effects such as exacerbation of articular diseases, endocrine disruption, and promotion of cancer. Previous studies have reported the role of this receptor in exacerbating RA in smokers and HQ-mediated cytotoxicity via activation of the AhR pathway in joint diseases. This study reports how HQ triggers the overexpression of AhR and its downstream effectors in the articular chondrocytes and mediates HQ catabolic effects.

Conclusion

Overall, these results indicate that xenobiotics and pollutants can have a direct influence on the health of the articular cartilage. The findings provide a detailed account of the detrimental effects of HQ exposure on articular cartilage homeostasis. It also sheds light on the manner in which environmental pollutants can worsen the degenerative effects of proinflammatory mechanisms that underlie articular disease onset.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources