Primary Human Chondrocytes Affected by Cigarette Smoke—Therapeutic Challenges

Abstract

Although several researchers have attested deleterious effects of smoking to the musculoskeletal system, the association between smoking and the onset of osteoarthritis (OA) remains unclear. Here, we investigate the effect of cigarette smoke extract (CSE) on primary human chondrocytes. The present study demonstrates that physiological concentrations of CSE (0.1%–10%) inhibit the viability, proliferation, and matrix formation of chondrocytes in a dose- and time-dependent manner. Significant amounts of free radicals were generated by 10% of CSE and led to cell death. A clinical dosage (4 mg/mL) of dexamethasone (Dex) showed toxic effects on chondrocytes, and the long-time treatment by lower doses (4–400 μg/mL) induced hypertrophic changes in the chondrocytes. To substitute Dex, diclofenac (Dic, 1 μg/mL) and acetaminophen (Ace, 10 μg/mL) were tested and did not worsen the metabolic activity of CSE-exposed chondrocytes. Hyaluronic acid (HA, 5 mg/mL) combined with Dic or Ace significantly inhibited the oxidative stress and enhanced the viability and matrix formation of CSE-exposed chondrocytes. This study shows for the first time that CSE mediates the disruption of cartilage through inducing cell death by increasing oxidative stress, and that this effect is fortified by Dex. The deleterious effects of CSE on chondrocytes could be reversed by treatment with HA combined with first-line analgesic/anti-inflammatory agents.

Adverse impact of smoking on the spine and spinal surgery

“…[ 23 ] In vitro studies show that cigarette smoke extract induces (in a dose- and time-dependent manner) impaired function and viability of chondrocytes found in articular cartilage. [ 7 ] The rheumatological and orthopedic literature reports increased articular cartilage loss and peripheral joint pain in smokers versus nonsmokers. [ 2 ] Further, smokers with osteoarthritis also have relatively decreased polymer molecular size and concentration of hyaluronic acid, critical for synovial joint lubrication.…”

“…[ 2 ] Further, smokers with osteoarthritis also have relatively decreased polymer molecular size and concentration of hyaluronic acid, critical for synovial joint lubrication. [ 7 ]…”

“…Mainstream cigarette smoke drawn into a smoker’s mouth consists of 8% tar and 92% gaseous components and contains thousands of toxic chemical compounds, about 10 15 free radicals per puff, and the addictive substance, nicotine. [ 1 , 7 , 13 ] Anti-smoking media campaigns usually emphasize the adverse health effects of cigarette smoking as including emphysema and chronic bronchitis, lung and other cancers, and cardiovascular diseases. [ 21 ] Here, the substantial negative impact of smoking on the spine and spinal surgery is emphasized, as cigarette smoke toxins compromise spinal blood flow and nutritional supply, [ 1 , 9 ] accelerate spondylosis, [ 12 ] and increase other surgical complications such as skin incision necrosis and dehiscence, delayed wound healing, and infection [ Table 1 ].…”

Maqui berry extract prevents cigarette smoke induced oxidative stress in human osteoblasts in vitro

“…CS is associated with a multitude of bone metabolism disorders and diseases, and one of the main mechanisms of CS-induced damage is the activation of oxidative stress. CS has been shown by our previous studies to induce oxidative stress in mesenchymal stem cells (Aspera-Werz et al, 2018[ 3 ]), chondrocytes (Chen et al, 2020[ 6 ]), and osteoblasts (Holzer et al, 2012[ 19 ]), thereby damaging the cells. The ROS level and nitrotyrosine are considered as important biomarkers of oxidative stress (Sun et al, 2019[ 47 ]).…”

“…hOBs which were exposed to 0.001 % v/v H 2 O 2 were considered as the positive control. The increase in fluorescence was detected by a plate reader (ex/em= 485/520 nm) (Chen et al, 2020[ 6 ]).…”