Dataset Information

Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.

ABSTRACT: Osteoarthritis (OA) is common age-associated disease, and associated with joint pain, mobility limitations and compromised overall quality of life. OA treatment is currently limited to pain management and joint arthroplasty at end stage disease. Oxidative damage to cartilage extracellular matrix and cells is an important mechanism in joint aging and OA pathogenesis. Evidence from in vitro and in vivo models of OA suggests that pharmaceuticals and natural compounds with antioxidant properties reduce expression of mediators of OA pathogenesis and OA severity in animal models. Among the signaling pathways that control cellular protective mechanisms against oxygen radical damage is heme oxygenase-1 (HO-1). We recently report HO-1 reduced OA severity in a mouse model. This led to the hypothesis that compounds that increase HO-1 expression have therapeutic potential in OA. Carnosic acid (CA), a natural diterpene with oxidant activity, is prevents cartilage degeneration though induction of HO-1. CA induced HO-1 and miR-140 expression in human articular chondrocytes, and cartilage degeneration was attenuated by CA treatment. Induced HO-1 by CA was in part associated with downregulation via miR-140 binding to 3'UTR of BTB and CNC homology 1 (BACH1). These findings suggest that CA attenuates cartilage degradation through HO-1 upregulation and has potential as a supplement for OA prevention.

SUBMITTER: Ishitobi H

PROVIDER: S-EPMC6240351 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.

Ishitobi Hiroyuki H Sanada Yohei Y Kato Yoshio Y Ikuta Yasunari Y Shibata Sachi S Yamasaki Satoshi S Lotz Martin K MK Matsubara Kiminori K Miyaki Shigeru S Adachi Nobuo N

European journal of pharmacology 20180417

Osteoarthritis (OA) is common age-associated disease, and associated with joint pain, mobility limitations and compromised overall quality of life. OA treatment is currently limited to pain management and joint arthroplasty at end stage disease. Oxidative damage to cartilage extracellular matrix and cells is an important mechanism in joint aging and OA pathogenesis. Evidence from in vitro and in vivo models of OA suggests that pharmaceuticals and natural compounds with antioxidant properties red ...[more]

PMID: 29678719

Similar Datasets

Project description:Heme oxygenase-1 (HO-1) can exert anti-inflammatory and antioxidant effects. Acute lung injury (ALI) is associated with increased inflammation and influx of proinflammatory cells and mediators in the airspaces and lung parenchyma. In this study, we demonstrate that pterostilbene 4'-?-glucoside (4-PG), the glycosylated form of the antioxidant pterostilbene (PTER), can protect against lipopolysaccharide- (LPS-) or Pseudomonas aeruginosa- (P. aeruginosa-) induced ALI when applied as a pretreatment or therapeutic post-treatment, via the induction of HO-1. To determine whether HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG, we subjected mice genetically deficient in Hmox-1 to LPS-induced ALI and evaluated histological changes, HO-1 expression, and proinflammatory cytokine levels in bronchoalveolar lavage (BAL) fluid. 4-PG exhibited protective effects on LPS- or P. aeruginosa-induced ALI by ameliorating pathological changes in lung tissue and decreasing proinflammatory cytokines. In addition, HO-1 expression was significantly increased by 4-PG in cells and in mouse lung tissues. The glycosylated form of pterostilbene (4-PG) was more effective than PTER in inducing HO-1 expression. Genetic deletion of Hmox-1 abolished the protective effects of 4-PG against LPS-induced inflammatory responses. Furthermore, we found that 4-PG decreased both intracellular ROS levels and mitochondrial (mt) ROS production in a manner dependent on HO-1. Pharmacological application of the HO-1 reaction product carbon monoxide (CO), but not biliverdin or iron, conferred protection in Hmox-1-deficient macrophages. Taken together, these results demonstrate that 4-PG can increase HO-1 expression, which plays a critical role in ameliorating intracellular and mitochondrial ROS production, as well as in downregulating inflammatory responses induced by LPS. Therefore, these findings strongly suggest that HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG.

Dataset Information

Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.

Publications

Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets